Self‐Mineralized Photothermal Bacteria Hybridizing with Mitochondria‐Targeted Metal–Organic Frameworks for Augmenting Photothermal Tumor Therapy

A photothermal bacterium (PTB) is reported for tumor‐targeted photothermal therapy (PTT) by using facultative anaerobic bacterium Shewanella oneidensis MR‐1 (S. oneidensis MR‐1) to biomineralize palladium nanoparticles (Pd NPs) on its surface without affecting bacterial activity. It is found that PTB possesses superior photothermal property in near infrared (NIR) regions, as well as preferential tumor‐targeting capacity. Zeolitic imidazole frameworks‐90 (ZIF‐90) encapsulating photosensitizer methylene blue (MB) are hybridized on the surface of living PTB to further enhance PTT efficacy. MB‐encapsulated ZIF‐90 (ZIF‐90/MB) can selectively release MB at mitochondria and cause mitochondrial dysfunction by producing singlet oxygen (¹O₂) under light illumination. Mitochondrial dysfunction further contributes to adenosine triphosphate (ATP) synthesis inhibition and heat shock proteins (HSPs) down‐regulated expression. The PTB‐based therapeutic platform of PTB@ZIF‐90/MB demonstrated here will find great potential to overcome the challenges of tumor targeting and tumor heat tolerance in PTT.     

Intracellular Nanoparticle Formation and Hydroxychloroquine Release for Autophagy-Inhibited Mild-Temperature Photothermal Therapy for Tumors

Mild-temperature photothermal therapy (PTT) of tumors has been intensively explored and adopted in preclinical/clinical trials in recent years. Nevertheless, tumor thermoresistance significantly compromises the therapeutic efficacy of mild-temperature PTT, and therefore, the extra addition of anti-thermoresistance agent is needed. Herein, by rational design of a peptide-hydroxychloroquine (HCQ) conjugate Cypate-Phe-Phe-Lys(SA-HCQ)-Tyr(H₂PO₃)-OH (Cyp-HCQ-Yp), a “smart” strategy of enzyme-triggered simultaneously intracellular photothermal nanoparticle formation and HCQ release is proposed for autophagy-inhibited mild-temperature PTT of tumor. In vitro results show that, under sequential catalysis of enzymes alkaline phosphatase and carboxylesterase, Cyp-HCQ-Yp is converted to Cypate-Phe-Phe-Lys(SA)-Tyr-OH (Cyp-Y) which self-assembles into its nanoparticle Cyp-NP and HCQ is released from Cyp-HCQ-Yp. By comparing with two control agents, it is validated that the exceptional therapeutic effect of Cyp-HCQ-Yp on tumor in vivo is achieved by its dual-enzyme-controlled intracellular nanoparticle formation and autophagy inhibition in tumors.     

Intracellular Bottom-up Synthesis of Ultrasmall CuS Nanodots in Cancer Cells for Simultaneous Photothermal Therapy and COX-2 Inactivation

The clinical application of photothermal therapy (PTT) is limited by the accuracy of thermal damage and the risk of tumor metastasis and relapse induced by hyperthermia-related inflammation. Intracellular bottom-up synthesis (iBuS) of CuS nanoparticles from small-molecule precursors inside tumor cells triggered by tumor specific stimuli is a promising strategy to enhance the precision of PTT treatment and reduce the risk of nondegradable metal nanoparticles. Herein, monolocking nanoparticles (MLNPs) with Cu-meloxicam complexes encapsulated by human serum albumin (HSA) are reported, which efficiently form CuS nanodots via the elevated concentration of endogenous H₂S inside tumor cells and meanwhile release meloxicam for anti-inflammatory effects. The intracellular bottom-up fabrication of CuS nanodots is directly visualized by TEM. An enhanced PTT effect is observed with 4T1 cells caused by additional meloxicam-induced inactivation of the COX-2 enzyme. After systemic administration, MLNPs completely ablate tumors under laser exposure, simultaneously inhibiting the inflammation induced by photothermal damage, and can be cleared via the kidney into urine. This strategy provides a new route for activated multimodal therapy, which could be applicable to precisely combat cancer.     

Hollow Nanostars with Photothermal Gold Caps and Their Controlled Surface Functionalization for Complementary Therapies

Gold nanoparticles exhibiting absorption in the desirable near‐infrared region are attractive candidates for photothermal therapy (PTT). Furthermore, the construction of one nanoplatform employing gold nanoparticles for complementary therapy is still a great challenge. Here, well‐defined unique hollow silica nanostars with encapsulated gold caps (starlike Au@SiO₂) are readily synthesized using a sacrificial template method. Ethanolamine‐functionalized poly(glycidyl methacrylate) (denoted as BUCT‐PGEA) brushes are then grafted controllably from the surface of starlike Au@SiO₂ nanoparticles via surface‐initiated atom transfer radical polymerization to produce starlike Au@SiO₂‐PGEA. The photothermal effect of gold caps with a cross cavity can be utilized for PTT. The interior hollow feature of starlike Au@SiO₂ nanoparticles endows them with excellent drug loading capability for chemotherapy, while the polycationic BUCT‐PGEA brushes on the surface provide good transfection performances for gene therapy, which will overcome the penetration depth limitation of PTT for tumor therapy. Compared with ordinary spherical Au@SiO₂‐PGEA counterparts, the starlike Au@SiO₂‐PGEA hybrids with sharp horns favor endocytosis, which can contribute to enhanced antitumor effectiveness. The rational integration of photothermal gold caps, hollow nanostars, and polycations through the facile strategy might offer a promising avenue for complementary cancer therapy.     

Pillar[5]arene-Modified Gold Nanorods as Nanocarriers for Multi-Modal Imaging-Guided Synergistic Photodynamic-Photothermal Therapy

Supramolecular approaches have opened up vast possibilities to construct versatile materials, especially those with stimuli-responsiveness and integrated functionalities of multi-modal diagnosis and synergistic therapeutics. In this study, a hybrid theranostic nanosystem named TTPY-Py⊂CP5@AuNR is constructed via facile host–guest interactions, where TTPY-Py is a photosensitizer with aggregation-induced emission and CP5@AuNR represents the carboxylatopillar[5]arene (CP5)-modified Au nanorods. TTPY-Py⊂CP5@AuNR integrates the respective advantages of TTPY-Py and CP5@AuNR such as the high performance of reactive oxygen species generation and photothermal conversion, and meanwhile shows fluorescence responses to both temperature and pH stimuli. The successful modification of CP5 macrocycles on AuNRs surfaces can eliminate the cytotoxicity of AuNRs and enable them to serve as the nanocarrier of TTPY-Py for further theranostic applications. Significantly, in vitro and in vivo evaluations demonstrate that this supramolecular nanotheranostic system possesses multiple modalities including intensive fluorescence imaging (FLI), photoacoustic imaging (PAI), efficient photodynamic therapy (PDT), and photothermal therapy (PTT), indicating its great potential for FLI-PAI imaging-guided synergistic PDT-PTT therapy. Moreover, TTPY-Py can be released upon activation by the acidic environment of lysosomes and then specifically light up mitochondria. This study demonstrates a new strategy for the design of versatile nanotheranostics for accurate tumor imaging and cancer therapies.     

Photostable Iodinated Silica/Porphyrin Hybrid Nanoparticles with Heavy‐Atom Effect for Wide‐Field Photodynamic/Photothermal Therapy Using Single Light Source

Physical therapies including photodynamic therapy (PDT) and photothermal therapy (PTT) can be effective against diseases that are resistant to chemotherapy and remain as incurable malignancies (for example, multiple myeloma). In this study, to enhance the treatment efficacy for multiple myeloma using the synergetic effect brought about by combining PDT and PTT, iodinated silica/porphyrin hybrid nanoparticles (ISP HNPs) with high photostability are developed. They can generate both ¹O₂ and heat with irradiation from a light‐emitting diode (LED), acting as photosensitizers for PDT/PTT combination treatment. ISP HNPs exhibit the external heavy atom effect, which significantly improves both the quantum yield for ¹O₂ generation and the light‐to‐heat conversion efficiency. The in vivo fluorescence imaging demonstrates that ISP HNPs, modified with folic acid and polyethylene glycol (FA‐PEG‐ISP HNPs), locally accumulate in the tumor after 18 h of their intravenous injection into tumor‐bearing mice. The LED irradiation on the tumor area of the mice injected with FA‐PEG‐ISP HNPs causes necrosis of the tumor tissues, resulting in the inhibition of tumor growth and an improvement in the survival rate.     

Amyloid Fibrils form Hybrid Colloidal Gels and Aerogels with Dispersed CaCO3 Nanoparticles

New hybrid colloidal gels are reported formed by amyloid fibrils and CaCO₃ nanoparticles (CaNPs), with Ca²⁺ as charge screening ions and CaNPs as physical crosslinking agents to establish and stabilize the network. The gel is characterized by rheological measurements and diffusing wave spectroscopy, complemented by microscopic observations using transmission and scanning electron microscopy. The hybrid colloidal gels show a two orders of magnitude improved gel strength at significantly shorter gelation times compared to previous calcium ion‐induced amyloid fibril gels. Supercritical CO₂‐dried colloidal aerogels allow demonstrating that amyloid fibrils, combined with smaller (higher specific surface area) CaNPs, constitute a denser fibrils network, resulting in stronger gels. By varying the amyloid fibril concentration and the CaNPs size and concentration, the complete phase diagram is mapped out. This enables identifying the sol–gel phase transition and a window for gel formation, which widens with increasing CaNPs size. Finally pH responsiveness and self‐healing properties of this hybrid colloidal gel are also demonstrated, making these systems a suitable candidate for biological applications.     

Immunotherapeutic Hydrogel with Photothermal Induced Immunogenic Cell Death and STING Activation for Post-Surgical Treatment

Post-surgical tumor recurrence remains a major clinical concern for patients with malignant solid tumors. Herein, an immunotherapeutic hydrogel (SA_PBA/ZMC/ICG) is developed by incorporating metal ion-cyclic dinucleotide (CDN) nanoparticles (Zn-Mn-CDN, ZMC) and a photosensitizer (indocyanine green, ICG) into phenylboronic acid (PBA)-conjugated sodium alginate (SA_PBA) for photothermal therapy (PTT)-triggered in situ vaccination to inhibit post-surgical recurrence and metastasis of malignant tumors. The gelation of SA_PBA/ZMC/ICG in the residual tumors can achieve accurate local PTT and the local sustained release of CDN and Mn²⁺ with minimal detrimental off-target toxic effects. Furthermore, CDN, which is an agonist of the stimulator of interferon genes (STING), along with Mn²⁺ can activate the STING pathway and trigger type-I-IFN-driven immune responses against tumors. Therefore, the immunotherapeutic hydrogel with enhanced immune response by STING agonist and PTT-induced immunogenic cell death (ICD) reprograms the post-surgical immunosuppressive microenvironment, substantially decreasing the post-surgical recurrence and metastasis of solid tumors in multiple murine tumor models when administered during surgical resection. Taken together, PTT-triggered and STING-mediated in situ cancer vaccination is an effective therapeutic intervention for post-surgical recurrence and metastasis of tumors.     

Fluorinated Polyethylenimine to Enable Transmucosal Delivery of Photosensitizer‐Conjugated Catalase for Photodynamic Therapy of Orthotopic Bladder Tumors Postintravesical Instillation

Photodynamic therapy (PDT) by insertion of an optical fiber into the bladder cavity has been applied in the clinic for noninvasive treatment of bladder tumors. To avoid systemic phototoxicity, bladder intravesical instillation of a photosensitizer may be an ideal approach for PDT treatment of bladder cancer, in comparison to conventional intravenous injection. However, the instillation‐based PDT for bladder cancer treatment remains to be less effective due to the poor urothelial uptake of photosensitizer, as well as the tumor hypoxia‐associated PDT resistance. Herein, it is uncovered that fluorinated polyethylenimine (F‐PEI) achieved by mixing with Chorin‐e6‐conjugated catalase (CAT‐Ce6) is able to form self‐assembled CAT‐Ce6/F‐PEI nanoparticles, which show greatly improved cross‐membrane, transmucosal, and intratumoral penetration capacities compared with CAT‐Ce6 alone or nonfluorinated CAT‐Ce6/PEI nanoparticles. Owing to the decomposition of tumor endogenous H₂O₂ by CAT‐Ce6/F‐PEI nanoparticles penetrating into bladder tumors, the tumor hypoxia would be effectively relieved to further favor PDT. Therefore, bladder intravesical instillation with CAT‐Ce6/F‐PEI nanoparticles could offer remarkably improved photodynamic therapeutic effect to destruct orthotopic bladder tumors with reduced systemic toxicity compared to hematoporphyrin, the first‐line photosensitizer used for bladder cancer PDT in clinic. This work presents a unique photosensitizer nanomedicine formulation, promising for clinical translation in instillation‐based PDT to treat bladder tumors.     

Nanomodulators Capable of Timely Scavenging ROS for Inflammation and Prognosis Control Following Photothermal Tumor Therapy

Despite the accuracy advantages of photothermal therapy (PTT), heat stress-initiated free radicals and damage-activated immune cells form a malignant positive feedback cycle following light irradiation. Herein, a 2D allomelanin nanomodulator with perpendicularly oriented oligomer planes is prepared by the guidance of DNA to achieve timely scavenging of reactive oxygen species (ROS) for inflammation and prognosis control following PTT. A large exposure degree of phenol groups and the effective transfer of delocalized electrons result in ultra-fast redox reactions that can be boosted by a self-amplifying process through structure disintegration. Compared with conventional photothermal agents, the nanodisks reduce the accumulation of ROS during PTT by 25-fold, downregulate the proinflammatory factors, and adjust inflammation levels to baseline. Thereby, successful modulation of M2-type macrophages in paratumor tissues significantly prevents burn wound progression and accelerates tissue repair, while well-controlled neutrophil extracellular traps and largely recruited CD4⁺/CD8⁺ T cells (1.6–3.2-fold) in the ablation site suppress the relapse of distant tumors. The study provides a useful inspiration on rationally modulating redox active nanostructures to address prognosis issues following PTT.     

Human HSP70 Promoter‐Based Prussian Blue Nanotheranostics for Thermo‐Controlled Gene Therapy and Synergistic Photothermal Ablation

Realizing precise control of the therapeutic process is crucial for maximizing efficacy and minimizing side effects, especially for strategies involving gene therapy (GT). Herein, a multifunctional Prussian blue (PB) nanotheranostic platform is first designed and then loaded with therapeutic plasmid DNA (HSP70‐p53‐GFP) for near‐infrared (NIR) light‐triggered thermo‐controlled synergistic GT/photothermal therapy (PTT). Due to the unique structure of the PB nanocubes, the resulting PB@PEI/HSP70‐p53‐GFP nanoparticles (NPs) exhibit excellent photothermal properties and pronounced tumor‐contrast performance in T₁/T₂‐weighted magnetic resonance imaging. Both in vitro and in vivo studies demonstrate that mild NIR‐laser irradiation (≈41 °C) activates the HSP70 promoter for tumor suppressor p53‐dependent apoptosis, while strong NIR‐laser irradiation (≈50 °C) induces photothermal ablation for cellular dysregulation and necrosis. Significant synergistic efficacy can be achieved by adjusting the NIR‐laser irradiation (from ≈41 to ≈50 °C), compared to using GT or PTT alone. In addition, in vitro and in vivo toxicity studies demonstrate that PB@PEI/HSP70‐p53‐GFP NPs have good biocompatibility. Therefore, this work provides a promising theranostic approach for controlling combined GT and PTT via the heat‐shock response.     

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.     

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.     

Enhanced Antitumor Efficacy by 808 nm Laser‐Induced Synergistic Photothermal and Photodynamic Therapy Based on a Indocyanine‐Green‐Attached W18O49 Nanostructure

A novel nanoplatform based on tungsten oxide (W₁₈O₄₉, WO) and indocyanine green (ICG) for dual‐modal photothermal therapy (PTT) and photodynamic therapy (PDT) has been successfully constructed. In this design, the hierarchical unique nanorod‐bundled W₁₈O₄₉ nanostructures play roles in being not only as an efficient photothermal agent for PTT but also as a potential nanovehicle for ICG molecules via electrostatic adsorption after modified with trimethylammonium groups on their surface. It is found that the ability of ICG to produce cytotoxic reactive oxygen species for PDT is well maintained after being attached on the WO, thus the as‐obtained WO@ICG can achieve a synergistic effect of combined PTT and PDT under single 808 nm near‐infrared (NIR) laser excitation. Notably, compared with PTT or PDT alone, the enhanced HeLa cells lethality of the 808 nm laser triggered dual‐modal therapy is observed. The in vivo animal experiments have shown that WO@ICG has effective solid tumor ablation effect with 808 nm NIR light irradiation, revealing the potential of these nanocomposites as a NIR‐mediated dual‐modal therapeutic platform for cancer treatment.     

PEGylated Micelle Nanoparticles Encapsulating a Non‐Fluorescent Near‐Infrared Organic Dye as a Safe and Highly‐Effective Photothermal Agent for In Vivo Cancer Therapy

Photothermal therapy (PTT), as a minimally invasive and highly effective cancer treatment approach, has received widespread attention in recent years. Tremendous effort has been devoted to explore various types of photothermal agents with high near‐infrared (NIR) absorbance for PTT cancer treatment. Despite many exciting progresses in the area, effective yet safe photothermal agents with good biocompatibility and biodegradability are still highly desired. In this work, a new organic PTT agent based on polyethylene glycol (PEG) coated micelle nanoparticles encapsulating a heptamethine indocyanine dye IR825 is developed, showing a strong NIR absorption band and a rather low quantum yield, for in vivo photothermal treatment of cancer. It is found that the IR825–PEG nanoparticles show ultra‐high in vivo tumor uptake after intravenous injection, and appear to be an excellent PTT agent for tumor ablation under a low‐power laser irradiation, without rendering any appreciable toxicity to the treated animals. Compared with inorganic nanomaterials and conjugated polymers being explored in PTT, the NIR‐absorbing micelle nanoparticles presented here may have the least safety concern while showing excellent treatment efficacy, and thus may be a new photothermal agent potentially useful in clinical applications.     

Bacteria‐Assisted Selective Photothermal Therapy for Precise Tumor Inhibition

Photothermal therapy (PTT) has drawn extensive research attention as a promising approach for tumor treatment. In this study, a bacteria‐assisted strategy relying on the selective reduction of perylene diimide derivative based supramolecular complex (CPPDI) to radical anions (RAs) by Escherichia coli in hypoxic tumors is developed to realize highly precise PTT of tumors. Noninvasive E. coli are first injected intravenously for selectively accumulating and replicating in the tumor due to the hypoxia tropism. Then, CPPDI is loaded in a peptide‐hybrid matrix metalloproteinase‐2 (MMP‐2) responsive liposome (MRL) and injected intravenously. After accumulated and released from MRL in the tumor where MMP‐2 is overexpressed, CPPDI is reduced by E. coli in the hypoxic tumor environment to produce CPPDI RAs (CRAs), which serve as effective photothermal agents for tumor cells thermal ablation under near‐infrared light irradiation. Since E. coli accumulate and grow in tumor sites selectively, this strategy accurately limits the production of CRAs in tumors for highly selective PTT, which will find great potential for precise tumor inhibition.     

Design and Synthesis of “All‐in‐One” Multifunctional FeS2 Nanoparticles for Magnetic Resonance and Near‐Infrared Imaging Guided Photothermal Therapy of Tumors

The ideal theranostic nanoplatform for tumors is a single nanoparticle that has a single semiconductor or metal component and contains all multimodel imaging and therapy abilities. The design and preparation of such a nanoparticle remains a serious challenge. Here, with FeS₂ as a model of a semiconductor, the tuning of vacancy concentrations for obtaining “all‐in‐one” type FeS₂ nanoparticles is reported. FeS₂ nanoparticles with size of ≈30 nm have decreased photoabsorption intensity from the visible to near‐infrared (NIR) region, due to a low S vacancy concentration. By tuning their shape/size and then enhancing the S vacancy concentration, the photoabsorption intensity of FeS₂ nanoparticles with size of ≈350 nm (FeS₂‐350) goes up with the increase of the wavelength from 550 to 950 nm, conferring the high NIR photothermal effect for thermal imaging. Furthermore, this nanoparticle has excellent magnetic properties for T₂‐weighted magnetic resonance imaging (MRI). Subsequently, FeS₂‐350 phosphate buffer saline (PBS) dispersion is injected into the tumor‐bearing mice. Under the irradiation of 915‐nm laser, the tumor can be ablated and the metastasis lesions in liver suffer significant inhibition. Therefore, FeS₂‐350 has great potential to be used as novel “all‐in‐one” multifunctional theranostic nanoagents for MRI and NIR dual‐modal imaging guided NIR‐photothermal ablation therapy (PAT) of tumors.     

An Acceptor–Donor–Acceptor Structured Small Molecule for Effective NIR Triggered Dual Phototherapy of Cancer

Dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is regarded as a more effective method for cancer treatment than single PDT or PTT. However, development of single component and near‐infrared (NIR) triggered agents for efficient dual phototherapy remains a challenge. Herein, a simple strategy to develop dual‐functional small‐molecules‐based photosensitizers for combined PDT and PTT treatment is proposed through: 1) finely modulating HOMO–LUMO energy levels to regulate the intersystem crossing (ISC) process for effective singlet oxygen (¹O₂) generation for PDT; 2) effectively inhibiting fluorescence via strong intramolecular charge transfer (ICT) to maximize the conversion of photo energy to heat for PTT or ISC process for PDT. An acceptor–donor–acceptor (A‐D‐A) structured small molecule (CPDT) is designed and synthesized. The biocompatible nanoparticles, FA‐CNPs, prepared by encapsulating CPDT directly with a folate functionalized amphipathic copolymer, present strong NIR absorption, robust photostability, cancer cell targeting, high photothermal conversion efficiency as well as efficient ¹O₂ generation under single 808 nm laser irradiation. Furthermore, synergistic PDT and PTT effects of FA‐CNPs in vivo are demonstrated by significant inhibition of tumor growth. The proposed strategy may provide a new approach to reasonably design and develop safe and efficient photosensitizers for dual phototherapy against cancer.     

Core–Satellite Mesoporous Silica–Gold Nanotheranostics for Biological Stimuli Triggered Multimodal Cancer Therapy

A core–satellite nanotheranostic agent with pH‐dependent photothermal properties, pH‐triggered drug release, and H₂O₂‐induced catalytic generation of radical medicine is fabricated to give a selective and effective tumor medicine with three modes of action. The nanocomplex (core–satellite mesoporous silica–gold nanocomposite) consists of amino‐group‐functionalized mesoporous silica nanoparticles (MSN‐NH₂) linked to L‐cysteine‐derivatized gold nanoparticles (AuNPs‐Cys) with bridging ferrous iron (Fe²⁺) ions. The AuNPs‐Cys serve as both removable caps that control drug release (doxorubicin) and stimuli‐responsive agents for selective photothermal therapy. Drug release and photothermal therapy are initiated by the cleavage of Fe²⁺ coordination bonds at low pH and the spontaneous aggregation of the dissociated AuNPs‐Cys. In addition, the Fe²⁺ is able to catalyze the decomposition of hydrogen peroxide abundant in cancer cells by a Fenton‐like reaction to generate high‐concentration hydroxyl radicals (·OH), which then causes cell damage. This system requires two tumor microenvironment conditions (low pH and considerable amounts of H₂O₂) to trigger the three therapeutic actions. In vivo data from mouse models show that a tumor can be completely inhibited after two weeks of treatment with the combined chemo‐photothermal method; the data directly demonstrate the efficiency of the MSN–Fe–AuNPs for tumor therapy.