Imaging‐Guided Combined Photothermal and Radiotherapy to Treat Subcutaneous and Metastatic Tumors Using Iodine‐131‐Doped Copper Sulfide Nanoparticles

Combining different therapeutic strategies to treat cancer by overcoming limitations of conventional cancer therapies has shown great promise in both fundamental and clinical studies. Herein, by adding ¹³¹I when making iodine‐doped CuS nanoparticles, CuS/[¹³¹I]I nanoparticles are obtained, which after functionalization with polyethylene glycol (PEG) are used for radiotherapy (RT) and photothermal therapy (PTT), by utilizing their intrinsic high near‐infrared absorbance and the doped ¹³¹I‐radioactivity, respectively. The combined RT and PTT based on CuS/[¹³¹I]I‐PEG is then conducted, achieving remarkable synergistic therapeutic effects as demonstrated in the treatment of subcutaneous tumors. In the meanwhile, as revealed by bimodal nuclear imaging and computed tomography (CT) imaging, it is found that CuS/[¹³¹I]I‐PEG nanoparticles after being injected into primary solid tumors could migrate to and retain in their nearby sentinel lymph nodes. Importantly, the combined RT and PTT applied on those lymph nodes to assist surgical resection of primary tumors results in remarkably inhibited cancer metastasis and greatly prolonged animal survival. In vivo toxicology studies further reveal that our CuS/I‐PEG is not obviously toxic to animals at fourfold of the treatment dose. This work thus demonstrates the potential of combining RT and PTT using a single nanoagent for imaging‐guided treatment of metastatic tumors.     

Ultralong Circulating Lollipop‐Like Nanoparticles Assembled with Gossypol,Doxorubicin, and Polydopamine via π–π Stacking for Synergistic Tumor Therapy

Long blood circulation in vivo remains a challenge to dual‐drug‐loaded nanocarriers for synergistic chemotherapy. Herein, a novel strategy to prepare lollipop‐like dual‐drug‐loaded nanoparticles (DOX–PDA–gossypol NPs) is developed based on the self‐assembly of gossypol, doxorubicin (DOX), and polydopamine (PDA) via π–π stacking. Dopamine polymerizes to PDA and fills the gaps between the gossypol and DOX molecules to form the super compact long‐circulating nanoparticles. The DOX–PDA–gossypol NPs show a suitable particle size of 59.6 ± 9.6 nm, high drug loading of 91%, superb stability, high maximum‐tolerated dose (MTD) of over 60 mg kg^‐1, and negligible toxicity. These NPs also exhibit pH‐dependent drug release and low combination index (0.23). Notably, they show dramatically ultralong blood circulation (>192 h) with elimination half times 458‐fold and 258‐fold longer than that of free DOX and free gossypol, respectively. These values are markedly higher than most of the reported results. Therefore, the DOX–PDA–gossypol NPs have a high tumor accumulation of 12% remaining on the 8th day postinjection. This characteristic contributes to the excellent tumor comprehensive synergistic therapeutic efficacy (TIR > 90%) with low administration dosage and is benefitted for widening the drug therapeutic window. Thus, the proposed strategy has remarkable potential for tumor synergistic therapy.     

Fabricating Aptamer‐Conjugated PEGylated‐MoS2/Cu1.8S Theranostic Nanoplatform for Multiplexed Imaging Diagnosis and Chemo‐Photothermal Therapy of Cancer

Fabricating theranostic nanoparticles combining multimode disease diagnosis and therapeutic has become an emerging approach for personal nanomedicine. However, the diagnostic capability, biocompatibility, and therapeutic efficiency of theranostic nanoplatforms limit their clinic widespread applications. Targeting to the theme of accurate diagnosis and effective therapy of cancer cells, a multifunctional nanoplatform of aptamer and polyethylene glycol (PEG) conjugated MoS₂ nanosheets decorated with Cu_1.8S nanoparticles (ATPMC) is developed. The ATPMC nanoplatform accomplishes photoluminescence imaging, photoacoustic imaging, and photothermal imaging for in vitro and in vivo tumor cells imaging diagnosis. Meanwhile, the ATPMC nanoplatform facilitates selective delivery of gene probe to detect intracellular microRNA aberrantly expressed in cancer cells and anticancer drug doxorubicin (DOX) for chemotherapy. Moreover, the synergistic interaction of MoS₂ and Cu_1.8S renders the ATPMC nanoplatform with superb photothermal conversion efficiency. The ATPMC nanoplatform loaded with DOX displays near‐infrared laser‐induced programmed chemotherapy and advanced photothermal therapy, and the targeted chemo‐photothermal therapy presents excellent antitumor efficiency.     

Near‐Infrared Absorbing Polymeric Nanoparticles as a Versatile Drug Carrier for Cancer Combination Therapy

Poly(3,4‐ethylenedioxythiophene):poly(4‐styrenesulfonate) (PEDOT:PSS) nanoparticles, after being coated with polyethylene glycol (PEG), are used as a drug carrier to load various types of aromatic therapeutic molecules, including chemotherapy drugs doxorubicin (DOX) and SN38, as well as a photodynamic agent chlorin e6 (Ce6), through π–π stacking and hydrophobic interaction. Interesting functionalities of PEDOT:PSS‐PEG as an unique versatile drug delivery platform are discovered. Firstly, for water‐insoluble drugs such as SN38, the loading on PEDOT:PSS‐PEG dramatically enhances its water solubility, while maintaining its cytotoxicity to cancer cells. Secondly, the delivery of Ce6 by PEDOT:PSS‐PEG is able to remarkably accelerate the cellular uptake of Ce6 molecules, and thus offers improved photodynamic therapeutic efficacy. Using DOX‐loaded PEDOT:PSS‐PEG as the model system, it is demonstrated that the photothermal effect of PEDOT:PSS‐PEG can be utilized to promote the delivery of this chemotherapeutic agent, achieving a combined photothermal‐ and chemotherapy with an obvious synergistic cancer killing effect. Moreover, it is also shown that multiple types of therapeutic agents could be simultaneously loaded on PEDOT:PSS‐PEG nanoparticles and delivered into cancer cells. This work highlights the great potential of NIR‐absorbing polymeric nanoparticles as multifunctional drug carriers for potential cancer combination therapy with high efficacy.     

A Low‐Toxic Multifunctional Nanoplatform Based on Cu9S5@mSiO2 Core‐Shell Nanocomposites: Combining Photothermal‐ and Chemotherapies with Infrared Thermal Imaging for Cancer Treatment

Copper chalcogenides have been demonstrated to be a promising photothermal agent due to their high photothermal conversion efficiency, synthetic simplicity, and low cost. However, the hydrophobic and less biocompatible characteristics associated with their synthetic processes hamper widely biological applications. An alternative strategy for improving hydrophilicity and biocompatibility is to coat the copper chalcogenide nanomaterials with silica shell. Herein, the rational preparation design results in successful coating mesoporous silica (mSiO₂) on as‐synthesized Cu₉S₅ nanocrystals, forming Cu₉S₅@mSiO₂‐PEG core‐shell nanostructures. As‐prepared Cu₉S₅@mSiO₂‐PEG core‐shell nanostructures show low cytotoxicity and excellent blood compatibility, and are effectively employed for photothermal ablation of cancer cells and infrared thermal imaging. Moreover, anticancer drug of doxorubicin (DOX)‐loaded Cu₉S₅@mSiO₂‐PEG core‐shell nanostructures show pH sensitive release profile and are therefore beneficial to delivery of DOX into cancer cells for chemotherapy. Importantly, the combination of photothermal‐ and chemotherapies demonstrates better effects of therapy on cancer treatment than individual therapy approaches in vitro and in vivo.     

Photo‐ and pH‐Triggered Release of Anticancer Drugs from Mesoporous Silica‐Coated Pd@Ag Nanoparticles

A smart drug delivery system integrating both photothermal therapy and chemotherapy for killing cancer cells is reported. The delivery system is based on a mesoporous silica‐coated Pd@Ag nanoplates composite. The Pd@Ag nanoplate core can effectively absorb and convert near infrared (NIR) light into heat. The mesoporous silica shell is provided as the host for loading anticancer drug, doxorubicin (DOX). The mesoporous shell consists of large pores, ～10 nm in diameter, and allows the DOX loading as high as 49% in weight. DOX loaded core–shell nanoparticles exhibit a higher efficiency in killing cancer cells than free DOX. More importantly, DOX molecules are loaded in the mesopores shell through coordination bonds that are responsive to pH and heat. The release of DOX from the core‐shell delivery vehicles into cancer cells can be therefore triggered by the pH drop caused by endocytosis and also NIR irradiation. A synergistic effect of combining chemotherapy and photothermal therapy is observed in our core‐shell drug delivery system. The cell‐killing efficacy by DOX‐loaded core–shell particles under NIR irradiation is higher than the sum of chemotherapy by DOX‐loaded particles and photothermal therapy by core–shell particles without DOX.     

An Injectable Supramolecular Polymer Nanocomposite Hydrogel for Prevention of Breast Cancer Recurrence with Theranostic and Mammoplastic Functions

The high locoregional breast cancer recurrence rate poses a significant risk for patients' survival. Injecting theranostic drugs‐laden soft tissue‐like hydrogels into the resected breast cavity is a promising strategy to achieve both precisely local therapy of breast cancer and reconstructive mammoplasty. In this work, a robust injectable thermoresponsive supramolecular poly(N‐acryloyl glycinamide‐co‐acrylamide) (PNAm) hydrogel bearing polydopamine (PDA) coated‐gold nanoparticles (AuNPs) and doxorubicin (DOX) is fabricated. The supramolecular polymer nanocomposite (SPN) hydrogels exhibit an excellent photothermal effect arising from PDA‐AuNPs that are tightly fixed to the hydrogel matrix via PDA and amide moieties in the network, built‐in near infrared (NIR) light‐triggered gel–sol transition as well as tunable drug delivery. The PNAm‐PDAAu‐DOX sol driven by prior heating is injected into the cavity of resected cancerous breasts of rats where gelation occurred rapidly while the temperature decreased to body temperature, thereby finely serving as a breast filler. During 4 week of implantation, interval NIR light irradiation can mediate photothermal effect and concertedly controllable DOX release, thus collectively preventing the recurrence of breast cancer. Remarkably, this stable remoldable SPN hydrogel facilitates the breast reconstruction and can be tracked by computed tomography (CT) imaging owing to the intrinsic X‐ray attenuation property of the loaded AuNPs.     

Redox‐Responsive and Drug‐Embedded Silica Nanoparticles with Unique Self‐Destruction Features for Efficient Gene/Drug Codelivery

The development of advanced gene/drug codelivery carriers with stimuli‐responsive release manner for complementary cancer therapy is desirable. In this study, novel disulfide‐bridged and doxorubicin (DOX)‐embedded degradable silica nanoparticles (DS‐DOX) with unique self‐destruction features are synthesized by a facile one‐pot method. In order to realize codelivery of genes and drugs, the surface of DS‐DOX nanoparticles is readily functionalized with the assembled polycation (CD‐PGEA), comprising one β‐cyclodextrin core and two ethanolamine‐functionalized poly(glycidyl methacrylate) arms, to achieve DS‐DOX‐PGEA. The redox‐responsive self‐destruction behavior of DS‐DOX imparts DS‐DOX‐PGEA with a better ability to release anticancer drug DOX, while the low‐toxic hydroxyl‐rich CD‐PGEA brushes can efficiently deliver genes for cancer treatment. Very interestingly, the degradation process of DS‐DOX starts from the outside, while the destruction of the degradable silica (DS) nanoparticles without DOX begins from the center of the nanoparticles. The embedded DOX inside the DS‐DOX nanoparticles can significantly influence the structures and facilitate the cellular uptake and the subsequent gene transfection. The as‐developed DS‐DOX‐PGEA nanostructure with coordinating biodegradability, stimuli‐responsiveness, and controlled release manner might be desirable gene/drug codelivery carriers for clinical cancer treatment.     

Multifunctional Core/Shell Nanoparticles Self‐Assembled from pH‐Induced Thermosensitive Polymers for Targeted Intracellular Anticancer Drug Delivery

Core/shell nanoparticles that display a pH‐sensitive thermal response, self‐assembled from the amphiphilic tercopolymer, poly(N‐isopropylacrylamide‐co‐N,N‐dimethylacrylamide‐co‐10‐undecenoic acid) (P(NIPAAm‐co‐DMAAm‐co‐UA)), have recently been reported. In this study, folic acid is conjugated to the hydrophilic segment of the polymer through the free amine group (for targeting cancer cells that overexpress folate receptors) and cholesterol is grafted to the hydrophobic segment of the polymer. This polymer also self‐assembles into core/shell nanoparticles that exhibit pH‐induced temperature sensitivity, but they possess a more stable hydrophobic core than the original polymer P(NIPAAm‐co‐DMAAm‐co‐UA) and a shell containing folate molecules. An anticancer drug, doxorubicin (DOX), is encapsulated into the nanoparticles. DOX release is also pH‐dependent. DOX molecules delivered by P(NIPAAm‐co‐DMAAm‐co‐UA) and folate‐conjugated P(NIPAAm‐co‐DMAAm‐co‐UA)‐g‐cholesterol nanoparticles enter the nucleus more rapidly than those transported by P(NIPAAm‐co‐DMAAm)‐b‐poly(lactide‐co‐glycolide) nanoparticles, which are not pH sensitive. More importantly, these nanoparticles can recognize folate‐receptor‐expressing cancer cells. Compared to the nanoparticles without folate, the DOX‐loaded nanoparticles with folate yield a greater cellular uptake because of the folate‐receptor‐mediated endocytosis process, and, thus, higher cytotoxicity results. These multifunctional polymer core/shell nanoparticles may make a promising carrier to target drugs to cancer cells and release the drug molecules to the cytoplasm inside the cells.     

Smart Ferrofluid with Quick Gel Transformation in Tumors for MRI‐Guided Local Magnetic Thermochemotherapy

Improved techniques for local administration of anticancer drugs are needed to reduce the side effects of chemotherapy owing to leakage of anticancer drugs from tumors and to enhance therapeutic efficacy. This study presents the development of smart ferrofluid that transforms immediately into a gel in tumors and generates heat in response to an alternating magnetic field (AMF), simultaneously releasing the anticancer drug. The smart ferrofluid, which is synthesized using less toxic magnetic materials (Fe₃O₄ nanoparticles), natural polysaccharides (alginate), and amino acids (cysteine), can also act as a contrast agent for magnetic resonance imaging (MRI). The ferrofluid also incorporates an anticancer drug (i.e., doxorubicin, DOX) via hydrogen bonds. AMF causes heating of gels prepared from the DOX‐containing ferrofluid, resulting in gel shrinkage and DOX release. In vivo experiments demonstrated that the ferrofluid transforms into a gel in the tumor, with the gel remaining in the tumor. Furthermore, magnetic thermochemotherapy using this ferrofluid inhibited tumor growth, while magnetic hyperthermia alone had only a marginal effect. Thus, the combination of magnetic hyperthermia and chemotherapy may be important for suppressing tumor growth. In summary, the ferrofluid presented here has the potential to facilitate MRI‐guided magnetic thermochemotherapy through a combination of endoscopic technologies in the future.     

NIR Light‐Triggered Degradable MoTe2 Nanosheets for Combined Photothermal and Chemotherapy of Cancer

Telluride molybdenum (MoTe₂) nanosheets with wide near‐infrared (NIR) absorbance are functionalized with polyethylene glycol‐cyclic arginine‐glycine‐aspartic acid tripeptide (PEG‐cRGD). After loading a chemotherapeutic drug (doxorubicin, DOX), MoTe₂‐PEG‐cRGD/DOX is used for combined photothermal therapy and chemotherapy. With the high photothermal conversion efficiency, MoTe₂‐PEG‐cRGD/DOX exhibits favorable cells killing ability under NIR irradiation. Owing to the cRGD‐mediated specific tumor targeting, MoTe₂‐PEG‐cRGD/DOX shows efficient accumulation in tumors to induce a strong tumor ablation effect. MoTe₂‐PEG‐cRGD nanosheets, which are relatively stable in the circulation, could be degraded under NIR ray. The in vitro and in vivo experimental results demonstrate that this theranostic nanoagent, which could accumulate in tumors to allow photothermal imaging and combined therapy, is readily degradable in normal organs to enable rapid excretion and avoid long‐term retention/toxicity, holding great potential to treat tumor effectively.     

One‐Pot Synthesis of Dual Stimulus‐Responsive Degradable Hollow Hybrid Nanoparticles for Image‐Guided Trimodal Therapy

Exploiting exogenous and endogenous stimulus‐responsive degradable nanoparticles as drug carriers can improve drug delivery systems (DDSs). The use of hollow nanoparticles may facilitate degradation, and combination of DDS with photodynamic therapy (PDT) and photothermal therapy (PTT) may enhance the anticancer effects of treatments. Here, a one‐pot synthetic method is presented for an anticancer drug (doxorubicin [DOX]) and photosensitizer‐containing hollow hybrid nanoparticles (HNPs) with a disulfide and siloxane framework formed in response to exogenous (light) and endogenous (intracellular glutathione [GSH]) stimuli. The hollow HNPs emit fluorescence within the near‐infrared window and allow for the detection of tumors in vivo by fluorescence imaging. Furthermore, the disulfides within the HNP framework are cleaved by intracellular GSH, deforming the HNPs. Light irradiation facilitates penetration of GSH into the HNP framework and leads to the collapse of the HNPs. As a result, DOX is released from the hollow HNPs. Additionally, the hollow HNPs generate singlet oxygen (¹O₂) and heat in response to light; thus, fluorescence imaging of tumors combined with trimodal therapy consisting of DDS, PDT, and PTT is feasible, resulting in superior therapeutic efficacy. Thus, this method may have several applications in imaging and therapeutics in the future.     

Biocompatible,Uniform, and Redispersible Mesoporous Silica Nanoparticles for Cancer‐Targeted Drug Delivery In Vivo

Engineering multifunctional nanocarriers for targeted drug delivery shows promising potentials to revolutionize the cancer chemotherapy. Simple methods to optimize physicochemical characteristics and surface composition of the drug nanocarriers need to be developed in order to tackle major challenges for smooth translation of suitable nanocarriers to clinical applications. Here, rational development and utilization of multifunctional mesoporous silica nanoparticles (MSNPs) for targeting MDA‐MB‐231 xenograft model breast cancer in vivo are reported. Uniform and redispersible poly(ethylene glycol)‐incorporated MSNPs with three different sizes (48, 72, 100 nm) are synthesized. They are then functionalized with amino‐β‐cyclodextrin bridged by cleavable disulfide bonds, where amino‐β‐cyclodextrin blocks drugs inside the mesopores. The incorporation of active folate targeting ligand onto 48 nm of multifunctional MSNPs (PEG‐MSNPs48‐CD‐PEG‐FA) leads to improved and selective uptake of the nanoparticles into tumor. Targeted drug delivery capability of PEG‐MSNPs48‐CD‐PEG‐FA is demonstrated by significant inhibition of the tumor growth in mice treated with doxorubicin‐loaded nanoparticles, where doxorubicin is released triggered by intracellular acidic pH and glutathione. Doxorubicin‐loaded PEG‐MSNPs48‐CD‐PEG‐FA exhibits better in vivo therapeutic efficacy as compared with free doxorubicin and non‐targeted nanoparticles. Current study presents successful utilization of multifunctional MSNP‐based drug nanocarriers for targeted cancer therapy in vivo.     

Cancer Cell Membrane‐Biomimetic Oxygen Nanocarrier for Breaking Hypoxia‐Induced Chemoresistance

The inadequate oxygen supply in solid tumor causes hypoxia, which leads to drug resistance and poor chemotherapy outcomes. To solve this problem, a cancer cell membrane camouflaged nanocarrier is developed with a polymeric core encapsulating hemoglobin (Hb) and doxorubicin (DOX) for efficient chemotherapy. The designed nanoparticles (DHCNPs) retain the cancer cell adhesion molecules on the surface of nanoparticles for homologous targeting and possess the oxygen‐carrying capacity of Hb for O₂‐interfered chemotherapy. The results show that DHCNPs not only achieve higher tumor specificity and lower toxicity by homologous targeting but also significantly reduce the exocytosis of DOX via suppressing the expressions of hypoxia‐inducible factor‐1α, multidrug resistance gene 1, and P‐glycoprotein, thus resulting in safe and high‐efficient chemotherapy. This work presents a new paradigm for targeted oxygen interference therapy by conquering hypoxia‐involved therapeutic resistance and achieves effective treatment of solid tumors.     

NIR‐Activated Supersensitive Drug Release Using Nanoparticles with a Flow Core

Near infrared (NIR) light‐activated supersensitive drug release via photothermal conversion is of particular interest due to its advantages in spatial and temporal control. However, such supersensitive drug release is rarely reported for polymeric nanoparticles. In this study, polymeric nanoparticles observed with flowable core can achieve NIR‐activated supersensitive drug release under the assistance of photothermal agent. It is demonstrated that only 5 s NIR irradiation (808 nm, 0.3 W cm^?2) leads to 17.8% of doxorubicin (DOX) release, while its release is almost completely stopped when the NIR laser is switched off. In contrast, the control, poly(d ,l ‐lactide) nanoparticles with rigid cores, do not exhibit such supersensitive effect. It is demonstrated that intraparticle temperature is notably increased during photothermal conversion by detecting fluorescein lifetime using a time‐correlated single photon counting (TCSPC) technique, which is the main driving force for such supersensitive drug release from hydrophobic flow core. In contrast, rigid chain of nanoparticular core hinders drug diffusion. Furthermore, such NIR light‐activated supersensitive drug release is demonstrated, which significantly enhances its anticancer efficacy, resulting in overcoming of the resistance of cancer cells against DOX treatment in vitro and in vivo. This simple and highly universal strategy provides a new approach to fabricate NIR light‐activated supersensitive drug delivery systems.     

Unprecedented “All‐in‐One” Lanthanide‐Doped Mesoporous Silica Frameworks for Fluorescence/MR Imaging and Combination of NIR Light Triggered Chemo‐Photodynamic Therapy of Tumors

Designing a single multifunctional nanoparticle that can simultaneously impart both diagnostic and therapeutic functions is considered to be a long‐lasting hurdle for biomedical researchers. Conventionally, a multifunctional nanoparticle can be constructed by integrating organic dyes/magnetic nanoparticles to impart diagnostic functions and anticancer drugs/photosensitizers to achieve therapeutic outcomes. These multicomponents systems usually suffer from severe photobleaching problems and cannot be activated by near‐infrared (NIR) light. Here, it is demonstrated that all‐in‐one lanthanide‐doped mesoporous silica frameworks (EuGdOx@MSF) loaded with an anticancer drug, doxorubicin (DOX) can facilitate simultaneous bimodal magnetic resonance (MR) imaging with approximately twofold higher T₁‐MR contrast as compared to the commercial Gd(III)‐DTPA complex and fluorescence imaging with excellent photostability. Upon a very low dose (130 mW cm^?2) of NIR light (980 nm) irradiation, the EuGdOx@MSF not only can sensitize formation of singlet oxygen (¹O₂) by itself but also can phototrigger the release of the DOX payload effectively to exert combined chemo‐photodynamic therapeutic (PDT) effects and destroy solid tumors in mice completely. It is also discovered for the first time that the EuGdOx@MSF‐mediated PDT effect can suppress the level of the key drug resistant protein, i.e., p‐glycoprotein (p‐gp) and help alleviate the drug resistant problem commonly associated with many cancers.     

Biomimetic Copper Sulfide for Chemo‐Radiotherapy: Enhanced Uptake and Reduced Efflux of Nanoparticles for Tumor Cells under Ionizing Radiation

Combined chemo‐radiotherapy is one of most widely applied treatments for clinical cancer therapy. Herein, it is found in this carefully designed study that ionizing radiation (e.g., X‐ray) can significantly increase the cell uptake of many different types of nanoparticles, and meanwhile obviously reduce their efflux. Such a phenomenon, which is not observed for small molecule drug such as doxorubicin (DOX), may be attributed to the X‐ray‐induced cell cycle change and upregulation of Caveolin‐1, a key protein in the caveolin‐dependent endocytosis pathway. Biomimetic copper sulfide nanoparticles, which are synthesized using melanin as the template and functionalized with polyethylene glycol (PEG), are then chosen as a platform for the combined chemo‐radiotherapy. Such CuS@Melanin‐PEG nanoparticles, while being able to load chemotherapeutics (e.g., DOX), can also act as a radiosensitizer to promote X‐ray induced cell apoptosis. In addition, although the overall tumor accumulation of CuS@Melanin‐PEG/DOX post intravenous injection is not significantly changed for tumors exposed to X‐ray, X‐ray radiation can result in obviously increased tumor cell uptake of drug‐loaded nanoparticles, subsequently leading to excellent synergistic antitumor therapeutic effect. A nanoplatform is developed with great performance in chemo‐radiotherapy, as well as uncovers a general synergistic mechanism particularly suitable for nanoparticle‐based chemo‐radiotherapy.     

Light‐Responsive,Singlet‐Oxygen‐Triggered On‐Demand Drug Release from Photosensitizer‐Doped Mesoporous Silica Nanorods for Cancer Combination Therapy

Smart drug delivery systems with on‐demand drug release capability are rather attractive to realize highly specific cancer treatment. Herein, a novel light‐responsive drug delivery platform based on photosensitizer chlorin e6 (Ce6) doped mesoporous silica nanorods (CMSNRs) is developed for on‐demand light‐triggered drug release. In this design, CMSNRs are coated with bovine serum albumin (BSA) via a singlet oxygen (SO)‐sensitive bis‐(alkylthio)alkene (BATA) linker, and then modified with polyethylene glycol (PEG). The obtained CMSNR‐BATA‐BSA‐PEG, namely CMSNR‐B‐PEG, could act as a drug delivery carrier to load with either small drug molecules such as doxorubicin (DOX), or larger macromolecules such as cis‐Pt (IV) pre‐drug conjugated third generation dendrimer (G3‐Pt), both of which are sealed inside the mesoporous structure of nanorods by BSA coating. Upon 660 nm light irradiation with a rather low power density, CMSNRs with intrinsic Ce6 doping would generate SO to cleave BATA linker, inducing detachment of BSA‐PEG from the nanorod surface and thus triggering release of loaded DOX or G3‐Pt. As evidenced by both in vitro and in vivo experiments, such CMSNR‐B‐PEG with either DOX or G3‐Pt loading offers remarkable synergistic therapeutic effects in cancer treatment, owing to the on‐demand release of therapeutics specifically in the tumor under light irradiation.     

Mesoporous Silica Coated Single‐Walled Carbon Nanotubes as a Multifunctional Light‐Responsive Platform for Cancer Combination Therapy

The development of cancer combination therapies, many of which rely on nanoscale theranostic agents, has received increasing attention in recent years. In this work, polyethylene glycol (PEG) modified mesoporous silica (MS) coated single‐walled carbon nanotubes (SWNTs) are fabricated and utilized as a multifunctional platform for imaging guided combination therapy of cancer. A model chemotherapy drug, doxorubicin (DOX), could be loaded into the mesoporous structure of the obtained SWNT@MS‐PEG nano‐carriers with high efficiency. Upon stimulation under near‐infrared (NIR) light, photothermally triggered drug release from DOX loaded SWNT@MS‐PEG is observed inside cells, resulting in a synergistic cancer cell killing effect. As revealed by both photoacoustic (PA) and magnetic resonance (MR) imaging, we further uncover efficient tumor accumulation of SWNT@MS‐PEG/DOX after intravenous injection into mice. In vivo combination therapy using this agent is further demonstrated in a mouse tumor model, achieving a remarkable synergistic anti‐tumor effect superior to that obtained by mono‐therapy. Our work presents a new type of theranostic nano‐platform, which could load therapeutic molecules with high efficiency, be responsive to external NIR stimulation, and at the same time serve as a diagnostic imaging agent.     

Bioactive Bacteria/MOF Hybrids Can Achieve Targeted Synergistic Chemotherapy and Chemodynamic Therapy against Breast Tumors

The hypoxic tumor microenvironment (TME) significantly affects cancer treatment. Conventional chemotherapeutic agents cannot effectively target hypoxic tumor tissue, which decreases efficacy and results in severe toxic side effects. To alleviate this problem, a self-driving biomotor is developed by functionalizing MCDP nanoparticles containing calcium peroxide and doxorubicin (DOX) loaded onto polydopamine-coated metal–organic frameworks（MOF）, with the anaerobic Bifidobacterium infantis (Bif) for synergistic chemotherapy and chemodynamic therapy (CDT) against breast cancer. The materials of institute Lavoisier (MIL) frameworks + CaO₂ + DOX + polydopamine (MCDP)@Bif biohybrid actively targets hypoxic regions of solid tumors via the inherent targeting ability of Bif. Once it has accumulated in the tumor tissue, MCDP generates hydroxyl radicals through the enhanced Fenton-type reactions between Fe²⁺ and self-generated hydrogen peroxide in the acidic TME. The disruption of Ca²⁺ homeostasis and resulting mitochondrial Ca²⁺ overload triggers apoptosis and enhances oxidative stress, promoting tumor cell death. The results found that the DOX concentration in MCDP@Bif-treated tumors is 3.8 times higher than that in free-DOX-treated tumors, which significantly prolongs the median survival of the tumor-bearing mice to 69 days and reduces the toxic side effects of DOX. Therefore, the novel bacteria-driven drug delivery system is highly effective in achieving synergistic chemotherapy and CDT against solid tumors.