Redox and pH Dual Responsive Polymer Based Nanoparticles for In Vivo Drug Delivery

Responsive nanomaterials have emerged as promising candidates as drug delivery vehicles in order to address biomedical diseases such as cancer. In this work, polymer‐based responsive nanoparticles prepared by a supramolecular approach are loaded with doxorubicin (DOX) for the cancer therapy. The nanoparticles contain disulfide bonds within the polymer network, allowing the release of the DOX payload in a reducing environment within the endoplasm of cancer cells. In addition, the loaded drug can also be released under acidic environment. In vitro anticancer studies using redox and pH dual responsive nanoparticles show excellent performance in inducing cell death and apoptosis. Zebrafish larvae treated with DOX‐loaded nanoparticles exhibit an improved viability as compared with the cases treated with free DOX by the end of a 3 d treatment. Confocal imaging is utilized to provide the daily assessment of tumor size on zebrafish larva models treated with DOX‐loaded nanoparticles, presenting sustainable reduction of tumor. This work demonstrates the development of functional nanoparticles with dual responsive properties for both in vitro and in vivo drug delivery in the cancer therapy.     

Multifunctional Upconversion Mesoporous Silica Nanostructures for Dual Modal Imaging and In Vivo Drug Delivery

Incorporating the agents for magnetic resonance imaging (MRI), optical imaging, and therapy in one nanostructured matrix to construct multifunctional nanomedical platform has attracted great attention for simultaneous diagnostic and therapeutic applications. In this work, a facile methodology is developed to construct a multifunctional anticancer drug nanocarrier by combining the special advantages of upconversion nanoparticles and mesoporous silica. β‐NaYF₄:Yb³⁺, Er³⁺@β‐NaGdF₄:Yb³⁺ is chosen as it can provide the dual modality of upconversion luminescence and MRI. Then mesoporous silica is directly coated onto the upconversion nanoparticles to form discrete, monodisperse, highly uniform, and core–shell structured nanospheres (labeled as UCNPs@mSiO₂), which are subsequently functionalized with hydrophilic polymer poly(ethylene glycol) (PEG) to improve the colloidal stability and biocompatibility. The obtained multifunctional nanocomposites can be used as an anticancer drug delivery carrier and applied for imaging. The anticancer drug doxorubicin (DOX) is absorbed into UCNPs@mSiO₂‐PEG nanospheres and released in a pH‐sensitive pattern. In vitro cell cytotoxicity tests on cancer cells verify that the DOX‐loaded UCNPs@mSiO₂‐PEG has comparable cytotoxicity with free DOX at the same concentration of DOX. In addition, the T₁‐weighted MRI that measures in aqueous solutions reveals that the contrast brightening increases with the concentration of Gd³⁺ component. Upconversion luminescence images of UCNPs@mSiO₂‐PEG uptaken by cells show green emission under 980 nm infrared laser excitation. Finally, the nanocomposites show low systematic toxicity and high in vivo antitumor therapy efficacy. These findings highlight the fascinating features of upconversion‐mesoporous nanocomposites as multimodality imaging contrast agents and nanocarrier for drug molecules.     

Gold Nanoparticle–Protein Agglomerates as Versatile Nanocarriers for Drug Delivery

The fabrication of a versatile nanocarrier based on agglomerated structures of gold nanoparticle (Au NP)–lysozyme (Lyz) in aqueous medium is reported. The carriers exhibit efficient loading capacities for both hydrophilic (doxorubicin) and hydrophobic (pyrene) molecules. The nanocarriers are finally coated with an albumin layer to render them stable and also facilitate their uptake by cancer cells. The interaction between agglomerated structures and the payloads is non‐covalent. Cell viability assay in vitro showed that the nanocarriers by themselves are non‐cytotoxic, whereas the doxorubicin‐loaded ones are cytotoxic, with efficiencies higher than that of the free drug. Transmission electron microscopy and fluorescence microscopy along with flow cytometry analysis confirm the uptake of the drug‐loaded nanocarriers by a human cervical cancer HeLa cell line. Field‐emission scanning electron microscopy reveals the formation of apoptotic bodies leading to cell death, confirming the release of the payloads from the nanocarriers into the cell. Overall, the findings suggest the fabrication of novel Au NP–protein agglomerate‐based nanocarriers with efficient drug‐loading and ‐releasing capabilities, enabling them to act as multimodal drug‐delivery vehicles.     

Chemo/Photoacoustic Dual Therapy with mRNA‐Triggered DOX Release and Photoinduced Shockwave Based on a DNA‐Gold Nanoplatform

A multifunctional nanoparticle based on gold nanorod (GNR), utilizing mRNA triggered chemo‐drug release and near‐infrared photoacoustic effect, is developed for a combined chemo‐photoacoustic therapy. The constructed nanoparticle (GNR‐DNA/FA:DOX) comprises three functional components: (i) GNR as the drug delivery platform and photoacoustic effect enhancer; (ii) toehold‐possessed DNA dressed on the GNR to load doxorubicin (DOX) to implement a tumor cell specific chemotherapy; and (iii) folate acid (FA) modified on GNR to guide the nanoparticle to target tumor cells. The results show that, upon an effective and specific delivery of the nanoparticles to the tumor cells with overexpressed folate receptors, the cytotoxic DOX loaded on the GNR‐DNA nanoplatform can be released through DNA displacement reaction in melanoma‐associated antigen gene mRNA expressed cells. With 808 nm pulse laser irradiation, the photoacoustic effect of the GNR leads to a direct physical damage to the cells. The combined treatment of the two modalities can effectively destroy tumor cells and eradicate the tumors with two distinctively different and supplementing mechanisms. With the nanoparticle, photoacoustic imaging is successfully performed in situ to monitor the drug distribution and tumor morphology for therapeutical guidance. With further in‐depth investigation, the proposed nanoparticle may provide an effective and safe alternative cancer treatment modality.     

Immune Cell‐Mediated Biodegradable Theranostic Nanoparticles for Melanoma Targeting and Drug Delivery

Although tremendous efforts have been made on targeted drug delivery systems, current therapy outcomes still suffer from low circulating time and limited targeting efficiency. The integration of cell‐mediated drug delivery and theranostic nanomedicine can potentially improve cancer management in both therapeutic and diagnostic applications. By taking advantage of innate immune cell's ability to target tumor cells, the authors develop a novel drug delivery system by using macrophages as both nanoparticle (NP) carriers and navigators to achieve cancer‐specific drug delivery. Theranostic NPs are fabricated from a unique polymer, biodegradable photoluminescent poly (lactic acid) (BPLP‐PLA), which possesses strong fluorescence, biodegradability, and cytocompatibility. In order to minimize the toxicity of cancer drugs to immune cells and other healthy cells, an anti‐BRAF V600E mutant melanoma specific drug (PLX4032) is loaded into BPLP‐PLA nanoparticles. Muramyl tripeptide is also conjugated onto the nanoparticles to improve the nanoparticle loading efficiency. The resulting nanoparticles are internalized within macrophages, which are tracked via the intrinsic fluorescence of BPLP‐PLA. Macrophages carrying nanoparticles deliver drugs to melanoma cells via cell–cell binding. Pharmacological studies also indicate that the PLX4032 loaded nanoparticles effectively kill melanoma cells. The “self‐powered” immune cell‐mediated drug delivery system demonstrates a potentially significant advancement in targeted theranostic cancer nanotechnologies.     

Boosting Interleukin‐12 Antitumor Activity and Synergism with Immunotherapy by Targeted Delivery with isoDGR‐Tagged Nanogold

The clinical use of interleukin‐12 (IL12), a cytokine endowed with potent immunotherapeutic anticancer activity, is limited by systemic toxicity. The hypothesis is addressed that gold nanoparticles tagged with a tumor‐homing peptide containing isoDGR, an αvβ3‐integrin binding motif, can be exploited for delivering IL12 to tumors and improving its therapeutic index. To this aim, gold nanospheres are functionalized with the head‐to‐tail cyclized‐peptide CGisoDGRG (Iso1) and murine IL12. The resulting nanodrug (Iso1/Au/IL12) is monodispersed, stable, and bifunctional in terms of αvβ3 and IL12‐receptor recognition. Low‐dose Iso1/Au/IL12, equivalent to 18–75 pg of IL12, induces antitumor effects in murine models of fibrosarcomas and mammary adenocarcinomas, with no evidence of toxicity. Equivalent doses of Au/IL12 (a nanodrug lacking Iso1) fail to delay tumor growth, whereas 15 000 pg of free IL12 is necessary to achieve similar effects. Iso1/Au/IL12 significantly increases tumor infiltration by innate immune cells, such as NK and iNKT cells, monocytes, and neutrophils. NK cell depletion completely inhibits its antitumor effects. Low‐dose Iso1/Au/IL12 can also increase the therapeutic efficacy of adoptive T‐cell therapy in mice with autochthonous prostate cancer. These findings indicate that coupling IL12 to isoDGR‐tagged nanogold is a valid strategy for enhancing its therapeutic index and sustaining adoptive T‐cell therapy.     

An Ultra pH‐Sensitive and Aptamer‐Equipped Nanoscale Drug‐Delivery System for Selective Killing of Tumor Cells

Nanotechnology has often been applied in the development of targeted drug‐delivery systems for the treatment of cancer. An ideal nanoscale system for drug delivery should be able to selectively deliver and rapidly release the carried therapeutic drug(s) in cancer cells and, more importantly, not react to off‐target cells so as to eliminate unwanted toxicity on normal tissues. To reach this goal, a selective chemotherapeutic is formulated using a hollow gold nanosphere (HAuNS) equipped with a biomarker‐specific aptamer (Apt), and loaded with the chemotherapy drug doxorubicin (DOX). The formed Apt‐HAuNS‐Dox, approximately 42 nm in diameter, specifically binds to lymphoma tumor cells and does not react to control cells that do not express the biomarker. Through aptamer‐mediated selective cell binding, the Apt‐HAuNS‐Dox is internalized exclusively into the targeted tumor cells, and then released the DOX intracellularly. Of note, although the formed Apt‐HAuNS‐Dox is stable under normal biological conditions (pH 7.4), it appears ultrasensitive to pH change and rapidly releases 80% of the loaded DOX within 2 h at pH 5.0, a condition seen in cell lysosomes. Functional assays using cell mixtures show that the Apt‐HAuNS‐Dox selectively kills lymphoma tumor cells, but has no effect on the growth of the off‐target cells in the same cultures, indicating that this ultra pH‐sensitive Apt‐HAuNS‐Dox can selectively treat cancer through specific aptamer guidance, and will have minimal side effects on normal tissue.     

Targeted combination therapy for glioblastoma by co-delivery of doxorubicin,YAP-siRNA and gold nanorods

The combination of brain targeting drug delivery systems and multi-modal intervention pose a promising therapeutic approach for glioblastoma therapy.In this study,we developed an angiopep-2 peptide modified cationic liposome loaded with doxorubicin,YAP-siRNA and gold nanorods(D/R@Ang2-Lip+Au)simultaneously,which has high encapsulating efficiency for doxorubicin(95.4%)and effective binding of siRNA at N/P ratio of 20:1.The fluorescence imaging and flow cytometry analysis revealed high cellular uptake of D/R@Ang2-Lip+Au.Real-time quantitative polymerase chain reaction and western blot analysis indicated that D/R@Ang2-Lip+Au could effectively inhibit the expression of YAP protein.In vitro and in vivo studies showed that D/R@Ang2-Lip+Au had the ability to target glioblastoma cells,and achieved better anti-proliferative effects compared with non-targeted D/R@Lip+Au.Moreover,in vivo experiment demonstrated that D/R@Ang2-Lip+Au was able to cross the blood-brain barrier,and combination therapy could significantly inhibit tumor growth.Therefore,the multifunctional D/R@Ang2-Lip+Au might provide a novel approach for effectively delivery of DOX,YAP-siRNA and AuNRs into the glioblastoma cells simultaneously and exerting synergistic therapeutic effects.     

Near‐Infrared Light Triggers Release of Paclitaxel from Biodegradable Microspheres: Photothermal Effect and Enhanced Antitumor Activity

Despite advances in controlled drug delivery, reliable methods for activatable, high‐resolution control of drug release are needed. The hypothesis that the photothermal effect mediated by a near‐infrared (NIR) laser and hollow gold nanospheres (HAuNSs) could modulate the release of anticancer agents is tested with biodegradable and biocompatible microspheres (1–15 µm) containing the antitumor drug paclitaxel (PTX) and HAuNSs (≈35 nm in diameter), which display surface plasmon absorbance in the NIR region. HAuNS‐containing microspheres exhibit a NIR‐induced thermal effect similar to that of plain HAuNSs. Rapid, repetitive PTX release from the PTX/HAuNS‐containing microspheres is observed upon irradiation with NIR light (808 nm), whereas PTX release is insignificant when the NIR light is switched off. The release of PTX from the microspheres is readily controlled by the output power of the NIR laser, duration of irradiation, treatment frequency, and concentration of HAuNSs embedded inside the microspheres. In vitro, cancer cells incubated with PTX/HAuNS‐loaded microspheres and irradiated with NIR light display significantly greater cytotoxic effects than cells incubated with the microspheres alone or cells irradiated with NIR light alone, owing to NIR‐light‐triggered drug release. Treatment of human U87 gliomas and MDA‐MB‐231 mammary tumor xenografts in nude mice with intratumoral injections of PTX/HAuNS‐loaded microspheres followed by NIR irradiation results in significant tumor‐growth delay compared to tumors treated with HAuNS‐loaded microspheres (no PTX) and NIR irradiation or with PTX/HAuNS‐loaded microspheres alone. The data support the feasibility of a therapeutic approach in which NIR light is used for simultaneous modulation of drug release and induction of photothermal cell killing.     

Monodisperse α-Fe(2)O(3)@SiO(2)@Au core/shell nanocomposite spheres: synthesis, characterization and properties

A new hybrid spherical structure α-Fe(2)O(3)@SiO(2)@Au with a size of about 141?nm was designed, with a hematite cubic core surrounded by a thick silica shell and further decorated with gold nanoparticles. The monodisperse α-Fe(2)O(3)@SiO(2) spheres were first prepared by a sol-gel process based on the modified St?ber method. Subsequently, the surface of the α-Fe(2)O(3)@SiO(2) particles was functionalized by-NH(2) functional groups. The electrostatic attraction of -NH(2) groups will attach the negatively charged Au nanoparticles to the amino-functionalized α-Fe(2)O(3)@SiO(2) nanospheres in order to prepare α-Fe(2)O(3)@SiO(2) monodisperse hybrid spheres. The M(H) hysteresis loop for α-Fe(2)O(3)@SiO(2) and α-Fe(2)O(3)@SiO(2)@Au spheres indicates that the nanocomposite spheres exhibit superparamagnetic characteristics at room temperature. The optical properties and the application of these hybrid nanocomposites as catalysts for the conversion of CO to CO(2) have also been studied.     

Programmed Nanoparticle‐Loaded Nanoparticles for Deep‐Penetrating 3D Cancer Therapy

Tumors are 3D, composed of cellular agglomerations and blood vessels. Therapies involving nanoparticles utilize specific accumulations due to the leaky vascular structures. However, systemically injected nanoparticles are mostly uptaken by cells located on the surfaces of cancer tissues, lacking deep penetration into the core cancer regions. Herein, an unprecedented strategy, described as injecting “nanoparticle‐loaded nanoparticles” to address the long‐lasting problem is reported for effective surface‐to‐core drug delivery in entire 3D tumors. The “nanoparticle‐loaded nanoparticle” is a silica nanoparticle (≈150 nm) with well‐developed, interconnected channels (diameter of ≈30 nm), in which small gold nanoparticles (AuNPs) (≈15 nm) with programmable DNA are located. The nanoparticle (AuNPs)‐loaded nanoparticles (silica): (1) can accumulate in tumors through leaky vascular structures by protecting the inner therapeutic AuNPs during blood circulation, and then (2) allow diffusion of the AuNPs for penetration into the entire surface‐to‐core tumor tissues, and finally (3) release a drug triggered by cancer‐characteristic pH gradients. The hierarchical “nanoparticle‐loaded nanoparticle” can be a rational design for cancer therapies because the outer large nanoparticles are effective in blood circulation and in protection of the therapeutic nanoparticles inside, allowing the loaded small nanoparticles to penetrate deeply into 3D tumors with anticancer drugs.     

Multistage Targeting Strategy Using Magnetic Composite Nanoparticles for Synergism of Photothermal Therapy and Chemotherapy

Mitochondrial‐targeting therapy is an emerging strategy for enhanced cancer treatment. In the present study, a multistage targeting strategy using doxorubicin‐loaded magnetic composite nanoparticles is developed for enhanced efficacy of photothermal and chemical therapy. The nanoparticles with a core–shell–SS–shell architecture are composed of a core of Fe₃O₄ colloidal nanocrystal clusters, an inner shell of polydopamine (PDA) functionalized with triphenylphosphonium (TPP), and an outer shell of methoxy poly(ethylene glycol) linked to the PDA by disulfide bonds. The magnetic core can increase the accumulation of nanoparticles at the tumor site for the first stage of tumor tissue targeting. After the nanoparticles enter the tumor cells, the second stage of mitochondrial targeting is realized as the mPEG shell is detached from the nanoparticles by redox responsiveness to expose the TPP. Using near‐infrared light irradiation at the tumor site, a photothermal effect is generated from the PDA photosensitizer, leading to a dramatic decrease in mitochondrial membrane potential. Simultaneously, the loaded doxorubicin can rapidly enter the mitochondria and subsequently damage the mitochondrial DNA, resulting in cell apoptosis. Thus, the synergism of photothermal therapy and chemotherapy targeting the mitochondria significantly enhances the cancer treatment.     

Synthesis and characterisation of liposomal doxorubicin with loaded gold nanoparticles

Developing nanostructures for cancer treatment is growing significantly. Liposomal doxorubicin is a drug that is used in the clinic and represents a lot of benefits over doxorubicin. The development of multifunctional liposomes with different cancer treatment capability enables broader applications of doxorubicin chemotherapy. Many efforts were carried to prepare more effective liposomal formulation through loading gold nanoparticles (GNPs) in the formulation. Here, GNPs with an average size of 6 nm were loaded in liposomal formulation alongside doxorubicin. The hydrodynamic diameter of final formulation was 177.3 ± 33.9 nm that in comparison with liposomes without GNPs (112.5 ± 10.3 nm), GNPs‐loaded liposomes showed the bigger hydrodynamic diameter. GNPs‐loaded liposomes are slightly positively charged (4.4 ± 1.1 mV), while liposomes without loading the GNPs were negatively charged (−18.5 ± 1.6 mV). Doxorubicin was loaded in this formulation through active loading technique. Doxorubicin loading efficiency in gold‐loaded liposomes is slightly lesser than liposomes without GNPs, but still considerably high in comparison to passive loading techniques.Inspec keywords: nanofabrication, drugs, nanomedicine, gold, cancer, lipid bilayers, drug delivery systems, nanoparticles, crystal growth from solutionOther keywords: liposomal doxorubicin, multifunctional liposomes, doxorubicin chemotherapy, active loading technique, doxorubicin loading efficiency, gold‐loaded liposomes, passive loading techniques, gold nanoparticles, cancer treatment, liposomal formulation, GNP‐loaded liposomes, hydrodynamic diameter     

A synergistically enhanced photothermal transition effect from mesoporous silica nanoparticles with gold nanorods wrapped in reduced graphene oxide

In this work, near-infrared (NIR)-responsive core–shell gold nanorods/mesoporous silica/reduced graphene oxide (Au/SiO₂/rGO) nanoparticles with synergistically enhanced photothermal stability and transition effect had been prepared via electrostatic interaction. Gold nanorods (AuNRs) and rGO were employed as the NIR-responsive components. UV–Vis–NIR extinction spectra revealed that the surface plasmon resonance peak of AuNRs from Au/SiO₂/rGO nanohybrids remained unchanged after 9 h NIR exposure. UV–Vis–NIR extinction results also showed that thin silica shell was superior to the thick ones in the photothermal stability improvement of Au/SiO₂/rGO nanoparticles. Moreover, the doxorubicin release of Au/SiO₂/rGO was more rapid than that of Au/SiO₂ upon NIR irradiation, indicating that synergistically enhanced photothermal effect between rGO and AuNRs endowed Au/SiO₂/rGO nanoparticles with excellent photothermal transition efficiency. Such novel NIR-responsive core–shell hybrid nanoparticles with enhanced photothermal stability and transition effect are well suited for further biological applications, such as photothermal therapy, bioimaging and drug delivery.     

Anti-cancer drug loaded iron-gold core-shell nanoparticles (Fe@Au) for magnetic drug targeting

Magnetic drug targeting, using core-shell magnetic carrier particles loaded with anti-cancer drugs, is an emerging and significant method of cancer treatment. Gold shell-iron core nanoparticles (Fe@Au) were synthesized by the reverse micelle method with aqueous reactants, surfactant, co-surfactant and oil phase. XRD, XPS, TEM and magnetic property measurements were utilized to characterize these core-shell nanoparticles. Magnetic measurements showed that the particles were superparamagnetic at room temperature and that the saturation magnetization decreased with increasing gold concentration. The anti-cancer drug doxorubicin (DOX) was loaded onto these Fe@Au nanoparticle carriers and the drug release profiles showed that upto 25% of adsorbed drug was released in 80 h. It was found that the amine (-NH2) group of DOX binds to the gold shell. An in vitro apparatus simulating the human circulatory system was used to determine the retention of these nanoparticle carriers when exposed to an external magnetic field. A high percentage of magnetic carriers could be retained for physiologically relevant flow speeds of fluid. The present findings show that DOX loaded gold coated iron nanoparticles are promising for magnetically targeted drug delivery.     

Simultaneous Imaging of Endogenous Survivin mRNA and On‐Demand Drug Release in Live Cells by Using a Mesoporous Silica Nanoquencher

The design of multifunctional drug delivery systems capable of simultaneous target detection, imaging, and therapeutics in live mammalian cells is critical for biomedical research. In this study, by using mesoporous silica nanoparticles (MSNs) chemically modified with a small‐molecule dark quencher, followed by sequential drug encapsulation, MSN capping with a dye‐labeled antisense oligonucleotide, and bioorthogonal surface modification with cell‐penetrating poly(disulfide)s, the authors have successfully developed the first mesoporous silica nanoquencher (qMSN), characterized by high drug‐loading and endocytosis‐independent cell uptake, which is able to quantitatively image endogenous survivin mRNA and release the loaded drug in a manner that depends on the survivin expression level in tumor cells. The authors further show that this novel drug delivery system may be used to minimize potential cytotoxicity encountered by many existing small‐molecule drugs in cancer therapy.     

A Gold Nanocage/Cluster Hybrid Structure for Whole‐Body Multispectral Optoacoustic Tomography Imaging,EGFR Inhibitor Delivery,and Photothermal Therapy

Gold nanocages (AuNCs) and gold nanoclusters (AuClusters) are two classes of advantageous nanostructures with special optical properties, and many other attractive properties. Integrating them into one nanosystem may achieve greater and smarter performance. Herein, a hybrid gold nanostructure for fluorescent and optoacoustic tomography imaging, controlled release of drugs, and photothermal therapy (PTT) is demonstrated. For this nanodrug (EA–AB), an epidermal growth factor receptor (EGFR) inhibitor erlotinib (EB) is loaded into AuNCs, which are then capped and functionalized by biocompatible AuCluster@BSA (BSA = bovine serum albumin) conjugates via electrostatic interaction. Upon cell internalization, the lysosomal proteases and low pH cause the release of EB from EA–AB, and also induce fluorescence restoration of the AuCluster for imaging. Irradiation with near‐infrared light further promotes the drug release and affords a PTT effect as well. The AuNC‐based nanodrug is optoacoustically active, and its biodistribution and metabolic process have been successfully monitored by whole‐body and 3D multispectral optoacoustic tomography imaging. Owing to the combined actions of PTT and EGFR pathway blockage, EA–AB exhibits marked tumor inhibition efficacy in vivo.     

Biodegradable Microalgae‐Based Carriers for Targeted Delivery and Imaging‐Guided Therapy toward Lung Metastasis of Breast Cancer

High delivery efficiency, prolonged drug release, and low systemic toxicity are effective weapons for drug delivery systems to win the battle against metastatic breast cancer. Herein, it is shown that Spirulina platensis (S. platensis) can be used as natural carriers to construct a drug‐loaded system for targeted delivery and fluorescence imaging‐guided chemotherapy on lung metastasis of breast cancer. The chemotherapeutic doxorubicin (DOX) is loaded into S. platensis (SP) via only one facile step to fabricate the DOX‐loaded SP (SP@DOX), which exhibits ultrahigh drug loading efficiency and PH‐responsive drug sustained release. The rich chlorophyll endows SP@DOX excellent fluorescence imaging capability for noninvasive tracking and real‐time monitoring in vivo. Moreover, the micrometer‐sized and spiral‐shaped SP carriers enable the as‐prepared SP@DOX to passively target the lungs and result in a significantly enhanced therapeutic efficacy on lung metastasis of 4T1 breast cancer. Finally, the undelivered carriers can be biodegraded through renal clearance without notable toxicity. The SP@DOX described here presents a novel biohybrid strategy for targeted drug delivery and effective treatment on cancer metastasis.     

Cyanine‐Anchored Silica Nanochannels for Light‐Driven Synergistic Thermo‐Chemotherapy

Smart nanoparticles are increasingly important in a variety of applications such as cancer therapy. However, it is still a major challenge to develop light‐responsive nanoparticles that can maximize the potency of synergistic thermo‐chemotherapy under light irradiation. Here, spatially confined cyanine‐anchored silica nanochannels loaded with chemotherapeutic doxorubicin (CS‐DOX‐NCs) for light‐driven synergistic cancer therapy are introduced. CS‐DOX‐NCs possess a J‐type aggregation conformation of cyanine dye within the nanochannels and encapsulate doxorubicin through the π–π interaction with cyanine dye. Under near‐infrared light irradiation, CS‐DOX‐NCs produce the enhanced photothermal conversion efficiency through the maximized nonradiative transition of J‐type Cypate aggregates, trigger the light‐driven drug release through the destabilization of temperature‐sensitive π–π interaction, and generate the effective intracellular translocation of doxorubicin from the lysosomes to cytoplasma through reactive oxygen species‐mediated lysosomal disruption, thereby causing the potent in vivo hyperthermia and intracellular trafficking of drug into cytoplasma at tumors. Moreover, CS‐DOX‐NCs possess good resistance to photobleaching and preferable tumor accumulation, facilitating severe photoinduced cell damage, and subsequent synergy between photothermal and chemotherapeutic therapy with tumor ablation. These findings provide new insights of light‐driven nanoparticles for synergistic cancer therapy.     

Semiconducting Polymer Nanocavities: Porogenic Synthesis,Tunable Host–Guest Interactions,and Enhanced Drug/siRNA Delivery

Nanocavities composed of lipids and block polymers have demonstrated great potential in biomedical applications such as sensors, nanoreactors, and delivery vectors. However, it remains a great challenge to produce nanocavities from fluorescent semiconducting polymers owing to their hydrophobic rigid polymer backbones. Here, we describe a facile, yet general strategy that combines photocrosslinking with nanophase separation to fabricate multicolor, water‐dispersible semiconducting polymer nanocavities (PNCs). A photocrosslinkable semiconducting polymer is blended with a porogen such as degradable macromolecule to form compact polymer dots (Pdots). After crosslinking the polymer and removing the porogen, this approach yields semiconducting polymer nanospheres with open cavities that are tunable in diameter. Both small molecules and macromolecules can be loaded in the nanocavities, where molecular size can be differentiated by the efficiency of the energy transfer from host polymer to guest molecules. An anticancer drug doxorubicin (Dox) is loaded into the nanocavities and the intracellular release is monitored in real time by the fluorescence signal. Finally, the efficient delivery of small interfering RNA (siRNA) to silence gene expression without affecting cell viability is demonstrated. The combined features of bright fluorescence, tunable cavity, and efficient drug/siRNA delivery makes these nanostructures promising for biomedical imaging and drug delivery.