A TME-enlightened protein-binding photodynamic nanoinhibitor for highly effective oncology treatment.

The efficiency of photodynamic therapy (PDT) is greatly dependent on intrinsic features of photosensitizers (PSs), but most PSs suffer from narrow diffusion distances and short life span of singlet oxygen (1O2). Here, to conquer this issue, we propose a strategy for in situ formation of complexes between PSs and proteins to deactivate proteins, leading to highly effective PDT. The tetrafluorophenyl bacteriochlorin (FBC), a strong near-infrared absorbing photosensitizer, can tightly bind to intracellular proteins to form stable complexes, which breaks through the space-time constraints of PSs and proteins. The generated singlet oxygen directly causes the protein dysfunction, leading to high efficiency of PSs. To enable efficient delivery of PSs, a charge-conversional and redox-responsive block copolymer POEGMA-b-(PAEMA/DMMA-co-BMA) (PB) was designed to construct a protein-binding photodynamic nanoinhibitor (FBC@PB), which not only prolongs blood circulation and enhances cellular uptake but also releases FBC on demand in tumor microenvironment (TME). Meanwhile, PDT-induced destruction of cancer cells could produce tumor-associated antigens which were capable to trigger robust antitumor immune responses, facilitating the eradication of residual cancer cells. A series of experiments in vitro and in vivo demonstrated that this multifunctional nanoinhibitor provides a promising strategy to extend photodynamic immunotherapy.

A H2 S-Generated Supramolecular Photosensitizer for Enhanced Photodynamic Antibacterial Infection and Relieving Inflammation.

Photodynamic therapy (PDT) is a promising treatment against bacteria-caused infections. By producing large amounts of reactive oxygen species (ROS), PDT can effectively eliminate pathogenic bacteria, without causing drug resistance. However, excessive ROS may also impose an oxidative stress on surrounding tissues, resulting in local inflammation. To avoid this major drawback and limit pro-inflammation during PDT, this work prepared a supramolecular photosensitizer (TPP-CN/CP5) based on host-guest interactions between a cysteine-responsive cyano-tetraphenylporphyrin (TPP-CN) and a water-soluble carboxylatopillar[5]arene (CP5). TPP-CN/CP5 not only possesses excellent photodynamic antibacterial properties, but also shows good anti-inflammatory and cell protection capabilities. Under 660 nm light irradiation, TPP-CN/CP5 could rapidly produce abundant ROS for sterilization. After the PDT process, the addition of cysteine (Cys) triggers the release of H2 S from TPP-CN. H2 S then stops the induced inflammation by inhibiting the production of related inflammatory factors. Both in vitro and in vivo experiments show the excellent antibacterial effects and anti-inflammatory abilities of TPP-CN/CP5. These results will certainly promote the clinical application of PDT in the treatment of bacterial infectious diseases.

A supramolecular nanoplatform for imaging-guided phototherapies via hypoxia tumour microenvironment remodeling.

Photodynamic therapy (PDT) has emerged as an invasive and promising antitumour treatment, however, the hypoxia in deep tumour tissues and the poor water-solubility of photosensitizers as bottlenecks greatly hinder PDT efficiency. Herein, a tumour microenvironment (TME) activated supramolecular nanoplatform consisting of the pillar[5]arene-based amphiphilic polymer POPD, the phototherapeutic agent Cy7-CN, respiratory medication atovaquone (ATO) and chemotherapeutic drug pyridinyl camptothecin (CPT-Py) was constructed for imaging-guided hypoxia-ameliorated phototherapies. Owing to host-guest interaction, the photochemical and photophysical properties of cyanine were improved exceedingly due to the suppression of π-π stacking. Triggered by the acidic microenvironment in tumour sites, the supramolecular nanoplatform would dissociate and release CPT-Py and ATO which inhibits mitochondria-associated oxidative phosphorylation (OXPHOS) and encourages more oxygen to be used in enhanced PDT. In vitro and in vivo studies verified that the rational combination of ATO-enhanced PDT and PTT overcame the disadvantages of single phototherapy and formed mutual promotion, and simultaneously sensitized chemotherapeutic drugs, which resulted in high tumour inhibition. It is hoped that the supramolecular nanoplatform could shed light on the development of phototherapeutic agents.

In situ generation of peroxynitrite (ONOO-) for enhanced antibacterial photodynamic therapy.

Antibacterial photodynamic therapy (PDT) as a valuable strategy to combat bacteria is always limited by its short lifespan, high oxygen dependence, and narrow therapeutic distance of the singlet oxygen generated through a Type-II reaction. Herein, we construct a photodynamic antibacterial nanoplatform (PDP@NORM) to produce oxygen-independent peroxynitrite (ONOO-) for achieving enhanced photodynamic antibacterial efficacy through the co-assembly of a nitric oxide (NO) donor and a porphyrin-based amphiphilic copolymer. ONOO- could be generated by the reaction of a superoxide anion radical () from the Type-I photodynamic process of porphyrin units with NO from the NO donor in PDP@NORM. The in vitro and in vivo experiments proved that PDP@NORM showed high antibacterial efficiency, resisting wound infection and speeding up wound healing after simultaneous irradiation with 650 nm and 365 nm light. Therefore, PDP@NORM may provide a new insight into the design of an efficient antibacterial strategy.

A Cascade BIME-Triggered Near-IR Cyanine Nanoplatform for Enhanced Antibacterial Photodynamic Therapy.

The long-standing misuse of antibiotics has accelerated the emergence of drug-resistant bacteria, which gives rise to an urgent public health threat. Antibacterial photodynamic therapy (aPDT), as a burgeoning and promising antibacterial strategy, plays an essential role in avoiding the evolution of drug-resistant microbes. However, it is hard for conventional photosensitizers to achieve satisfactory antibacterial efficacy because of the complex bacterial infectious microenvironment (BIME). Herein, a cascade BIME-triggered near-infrared cyanine (HA-CY) nanoplatform has been developed via conjugating cyanine units to biocompatible hyaluronic acid (HA) for enhanced aPDT efficacy. The HA-CY nanoparticles can be dissociated under the overexpressed hyaluronidase in BIME to release a cyanine photosensitizer. Meanwhile, cyanine can be protonated under acidic BIME, where protonated cyanine can efficiently adhere to the surface of a negatively charged bacterial membrane and increase singlet oxygen production due to intramolecular charge transfer (ICT). Experiments in the cellular level and animal model proved that the BIME-triggered activation of aPDT could remarkably boost aPDT efficacy. Overall, this BIME-triggered HA-CY nanoplatform presents great promise for overcoming the dilemma of drug-resistant microbes.

Inflammation specific environment activated methotrexate-loaded nanomedicine to treat rheumatoid arthritis by immune environment reconstruction.

Rheumatoid arthritis (RA), as an autoimmune inflammatory disease, is featured by enhanced vascular permeability, irreversible cartilage destroys and bone erosion. Although the pathogenesis of RA is still unclear, the immune environment, particularly the lymphatic system, which is instrumental to immune cell surveillance and interstitial fluid balance, plays vital roles in the process of RA. Herein, an inflammation specific environment activated methotrexate-encapsulated nanomedicine (MTX@NPs) was constructed for RA treatment, which accumulated in inflamed joints, and released MTX in the specific RA microenvironment. Notably, MTX@NPs could regulate the immune environment including reducing the expressions of inflammatory cytokines of macrophages and the inflammatory level of lymphatic epithelial cells (LECs), and ameliorating the lymphatic vessel contraction and drainage. In vitro and In vivo studies illustrated that MTX@NPs exhibited a high RA therapeutic efficacy and insignificant systemic toxicity owing to the suppression of the inflammation response and the improved lymphatic functions of RA joints. It suggests that the nanomedicine paves a potential way to the clinical practice of autoimmune diseases treatments via the regulation of immune environment and lymphatic functions. STATEMENT OF SIGNIFICANCE: Although 1.0% of the population in the world suffers from rheumatoid arthritis (RA), the pathogenesis of RA is still unclear and the therapeutic effect of the first-line clinical drugs is relatively low. Herein, we propose a specific RA-microenvironment triggered nanomedicine (MTX@NPs), which enhances RA treatment of a first-line antirheumatic drug (methotrexate, MTX) by immune environment reconstruction. The nanomedicine exhibits RA joints accumulation by EPR effect, and releases MTX under the specific RA environment, leading to the dramatical drop of M1-type macrophages and acceleration of lymphatic vessel contraction and drainage. Finally, the inflammatory cytokines in RA immune environment are reduced sharply, indicating the outstanding therapeutic efficacy of MTX@NPs to RA.

Highly Antibacterial and Adhesive Hyaluronic Acid Hydrogel for Wound Repair.

Bacterial infections accompanied with wound healing often lead to more serious health hazards to patients. Therefore, it is urgent to explore a wound dressing that can promote wound repair while possessing antibacterial capability. Here, we constructed a multifunctional hydrogel dressing by a redox-initiated cross-linking reaction of methacrylated hyaluronic acid (HAMA), 5,10,15,20-tetra (4-methacrylate phenyl) porphyrin (TPP), and dopamine methacrylamide (DMA), named HAMA-TPP-DMA, with broad-spectrum photodynamic antibacterial capability, where the aggregation of TPP photosensitizer units could be greatly inhibited to produce more singlet oxygen. The hydrogel has excellent biodegradability and biocompatibility, providing favorable conditions for wound healing. Furthermore, the incorporation of dopamine into the hydrogel gives the wound dressing with enhanced adhesiveness, benefiting for the wound repair. More importantly, the antibacterial experiments in vitro and mice wound models in vivo showed that the HAMA-TPP-DMA hydrogel can significantly resist bacteria and accelerate the wound healing in mice (the closure rate > 98% after 15 days). Thus, this hydrogel dressing with superior antibacterial infection and wound healing capability provides a promising strategy in wound repair.

A carboxylatopillar[5]arene-based pH-triggering supramolecular photosensitizer for enhanced photodynamic antibacterial efficacy.

A pH-triggering supramolecular antibacterial photosensitizer was constructed by host-guest interaction between a water-soluble porphyrin photosensitizer and carboxylatopillar[5]arene (P[5]). The formation of the supramolecular complex not only improves the biocompatibility of the photosensitizer, but also enhances antibacterial efficacy by pH-triggering dissociation under the low pH bacterial microenvironment.

Oxygen-Carrying and Antibacterial Fluorinated Nano-Hydroxyapatite Incorporated Hydrogels for Enhanced Bone Regeneration.

Insufficient oxygen availability in tissue engineering is one of the major factors for the failure of clinical transplantation. One potential strategy to conquer this limitation is the fabrication of spontaneous and continuous oxygen supplying scaffolds for in situ tissue regeneration. In this work, a versatile fluorine-incorporating hydrogel is designed which can not only timely and continuously supply oxygen for mesenchymal stem cells (MSCs) to overcome deficient oxygen before vascularization in scaffolds, but can present a higher antibacterial capability to avoid bacterial infections. The HAp@PDA-F nanoparticles are first prepared and then incorporated with the quaternized and methacrylated chitosan forming CS/HAp@PDA-F by photo-crosslinking. In vitro results indicate that CS/HAp@PDA-F hydrogel has outstanding mechanical performance, moreover, it also has the oxygen-carrying ability to prolong survival ability, enhance proliferation activity, and preserve osteogenic differentiation potency and promote osteogenic-related genes expression of rat bone mesenchymal stem cells (rBMSCs) under hypoxic environment. Furthermore, the CS/HAp@PDA-F hydrogel can inhibit the growth of Staphylococcus aureus and Escherichia coli, providing a good antibacterial activity. Additionally, in vivo experiments demonstrate higher bone volume and bone mineral density, and more new bone tissue generation in CS/HAp@PDA-F group than in CS/HAp@PDA group. These results indicate that the rational design of fluorinated hydrogel possesses a good clinical application prospect for bone regeneration.

Mitochondria-targeting and ROS-sensitive smart nanoscale supramolecular organic framework for combinational amplified photodynamic therapy and chemotherapy.

Owing to their reversibly dynamic features, and the regularity of their architectures, supramolecular organic frameworks (SOFs) have attracted attention as new porous materials. Herein, we propose a smart SOF platform for enhanced photodynamic therapy, where the SOF with a superior mitochondria-targeting capability could be cleaved by reactive oxygen species (ROS) produced by itself for highly enhancing PDT. Moreover, it can further work as a platform for carrying chemo-therapeutic drug doxorubicin for synergistic chemo-photodynamic therapy. The SOF is constructed by combining a tetra-ß-cyclodextrin-conjugated porphyrin photosensitizer and a ROS-sensitive thioketal linked adamantane dimer utilizing a host-guest supramolecular strategy. The unique supramolecular framework not only completely resolves the aggregation caused quenching of porphyrin photosensitizers but also endows them with significantly enhanced water-solubility. The in vitro and in vivo results demonstrate that the SOF could be targeted onto mitochondria by confocal imaging, and dissociated by ROS generated by itself, leading to autonomous release of porphyrin photosensitizers and DOX for high anti-cancer activity. It is believed that the strategy using a SOF has the potential of being used to construct versatile agents for combined therapies. STATEMENT OF SIGNIFICANCE: Photosensitizers are the essential element in photodynamic therapy. However, typical photosensitizers commonly encounter poor water-solubility, non-specific tumor-targeting, aggregation-caused quenching (ACQ), which seriously reduce PDT efficacy. A mitochondria-targeting and ROS-sensitive supramolecular organic framework (SOF) is designed for photodynamic therapy in cancer treatment, which could completely overcome the bottleneck in the applications of photosensitizers (PSs). The SOF is constructed by combining a tetra-ß-cyclodextrin-conjugated porphyrin photosensitizer and a ROS-sensitive thioketal linked adamantane dimer unit utilizing a host-guest supramolecular strategy. The unique supramolecular framework not only completely resolves the aggregation caused quenching of porphyrin photosensitizers but also endows them with significantly enhanced water-solubility. Moreover, the SOF can be readily functionalized to incorporate the anti-cancer agent Doxorubicin and mitochondria targeting molecules through respective physical encapsulation and host-guest interactions.

Zeolitic Imidazolate Framework Platform for Combinational Starvation Therapy and Oxygen Self-Sufficient Photodynamic Therapy against a Hypoxia Tumor.

The antitumor efficacy of photodynamic therapy (PDT) is greatly impeded by the nonspecific targeting of photosensitizers and limited oxygen supply in hypoxic tumors. Aiming to overcome the problem, a dual-locked porphyrin/enzyme-loading zeolitic imidazolate framework (ZIF) nanoplatform was constructed for starvation therapy and O2 self-sufficient PDT. The fluorescence recovery and PDT of photosensitizers could be cooperatively triggered by dual pathological parameters, the low pH and overexpressed GSH in tumor tissues, which makes the PDT process conduct precisely in a tumor microenvironment. The cascade catalysis of glucose oxidase and catalase promotes the nanoplatform dissociation, inhibits the energy supply of tumors (starvation therapy), and provides enough O2 to ameliorate the hypoxia and enhance PDT efficacy. In vitro and in vivo studies were performed to confirm the high antitumor efficacy of the porphyrin/enzyme-loading ZIF nanoplatform. Thus, this work offers a path for precise and efficient PDT-based combination therapy against a hypoxia tumor.

Pillar[5]arene-Based Switched Supramolecular Photosensitizer for Self-Amplified and pH-Activated Photodynamic Therapy.

Photodynamic therapy (PDT) has emerged as a promising and spatiotemporally controllable cancer treatment modality. However, serious skin photosensitization during the PDT process limits the clinical application of PDT. Thus, the construction of "smart" and multifunctional photosensitizers has attracted substantial interest. Herein, we develop a mitochondria-targeting and pH-switched hybrid supramolecular photosensitizer by the host-guest interaction. The PDT efficacy of supramolecular photosensitizers can be quenched by the Förster resonance energy transfer (FRET) effect during long circulation and activated by the dissociation of supramolecular photosensitizers in an acidic tumor microenvironment, benefitting from the dynamic feature of the host-guest interaction and pH responsiveness of the water-soluble pillar[5]arene on gold nanoparticles. The rational integration of mitochondria-targeting and reductive glutathione (GSH) elimination in the hybrid switchable supramolecular photosensitizer prolongs the lifetime of reactive oxygen species generated in the PDT near mitochondria and further amplifies the PDT efficacy. Thus, the facile and versatile construction of switchable supramolecular photosensitizer offers not only the targeted and precise phototherapy but also high therapeutic efficacy, which would provide a new path for the clinic application of PDT.

Enhanced photodynamic therapy through supramolecular photosensitizers with an adamantyl-functionalized porphyrin and a cyclodextrin dimer.

A supramolecular photosensitizer was constructed using a tetra-adamantane-functionalized porphyrin and a dimer of permethyl-ß-cyclodextrin through host-guest interaction and self-assembly. The porphyrin/cyclodextrin alternating structure of supramolecular photosensitizers not only enhances the water solubility of the photosensitizers, but also effectively inhibits the aggregation-induced quenching of porphyrin photosensitizers.

Linear Alternating Supramolecular Photosensitizer for Enhanced Photodynamic Therapy.

Supramolecular polymers with facile and versatile architectures via noncovalent connection present great potential in biological fields. Herein, a linear alternating supramolecular polymer is constructed via host-guest inclusion interaction between cyclodextrin dimer (CD2) and bifunctional adamantane-conjugated porphyrin (TPP-Ad2). The supramolecular alternating structure of CD/TPP could not only suppress the aggregation of PSs to improve the photophysical properties because of the steric hindrance but also enhance the water solubility of PSs induced from cyclodextrin moieties. The nanoplatform obtained by this linear alternating supramolecular polymer (TPP-Ad2/CD2) presents significantly enhanced photodynamic therapy (PDT) efficacy, providing a promising path for PDT.

Janus macromolecular brushes for synergistic cascade-amplified photodynamic therapy and enhanced chemotherapy.

The aggregation-caused quenching (ACQ) effect of photosensitizers and multidrug resistance are the major obstacles in photodynamic therapy (PDT) and chemotherapy, respectively. Synergistic photo-chemotherapy is a promising cancer treatment to overcome the short boards of each single therapy. However, the fabrication of nanocarriers acting as both photosensitizers in PDT and the vehicle of drug release is a key challenge. Herein, we constructed a well-defined porphyrin-containing Janus macromolecular brush and used it as both a photosensitizer and a pH-responsive vehicle for DOX release. The Janus macromolecular brush with pH-responsive side chains and porphyrin units linked covalently in each repeat unit was synthesized by the combination of reversible addition-fragmentation chain transfer (RAFT) polymerization and click chemistry. The high grafting content of porphyrin units in the macromolecular brush improved the DOX loading capability by π-π stacking and therefore reduced the total treatment dose of DOX-loaded macromolecular brush nanoparticles (NPs). The pH-responsive side chains played triple roles in synergistic cascade-amplified PDT and enhanced chemotherapy including an executor of controlled drug release, a ligand with a mitochondria-targeting feature, and a barrier to reduce the ACQ effect of porphyrin units. In vitro and in vivo studies confirmed that the DOX-loaded macromolecular brush NPs exhibited high phototoxicity and significant tumor inhibition efficacy. STATEMENT OF SIGNIFICANCE: Synergistic photodynamic therapy (PDT) and chemotherapy has emerged as a promising cancer treatment to overcome the challenges of a single modality. Herein, we constructed new pH-responsive vesicles using porphyrin-containing Janus macromolecular brushes as theranostic nanocarriers to encapsulate high-loading doxorubicin (DOX) for synergistic cascade-amplified PDT and enhanced chemotherapy. The high grafting content of porphyrin units in Janus macromolecular brushes improved DOX loading capability by π-π stacking for enhanced chemotherapy. Moreover, pH-responsive side chains subsequently enhanced the suppression of the aggregation-caused quenching (ACQ) effect of porphyrins for cascade-amplified PDT. In vitro and in vivo studies confirmed that DOX-loaded macromolecular brush nanoparticles exhibited high phototoxicity and significant tumor inhibition efficacy.

Novel nanomedicine with a chemical-exchange saturation transfer effect for breast cancer treatment in vivo.

BACKGROUND: Nanomedicine is a promising new approach to cancer treatment that avoids the disadvantages of traditional chemotherapy and improves therapeutic indices. However, the lack of a real-time visualization imaging technology to monitor drug distribution greatly limits its clinical application. Image-tracked drug delivery is of great clinical interest; it is useful for identifying those patients for whom the therapy is more likely to be beneficial. This paper discusses a novel nanomedicine that displays features of nanoparticles and facilitates functional magnetic resonance imaging but is challenging to prepare. RESULTS: To achieve this goal, we synthesized an acylamino-containing amphiphilic block copolymer (polyethylene glycol-polyacrylamide-polyacetonitrile, PEG-b-P(AM-co-AN)) by reversible addition-fragmentation chain transfer (RAFT) polymerization. The PEG-b-P(AM-co-AN) has chemical exchange saturation transfer (CEST) effects, which enable the use of CEST imaging for monitoring nanocarrier accumulation and providing molecular information of pathological tissues. Based on PEG-b-P(AM-co-AN), a new nanomedicine PEG-PAM-PAN@DOX was constructed by nano-precipitation. The self-assembling nature of PEG-PAM-PAN@DOX made the synthesis effective, straightforward, and biocompatible. In vitro studies demonstrate decreased cytotoxicity of PEG-PAM-PAN@DOX compared to free doxorubicin (half-maximal inhibitory concentration (IC50), mean ~ 0.62 µg/mL vs. ~ 5 µg/mL), and the nanomedicine more efficiently entered the cytoplasm and nucleus of cancer cells to kill them. Further, in vivo animal experiments showed that the nanomedicine developed was not only effective against breast cancer, but also displayed an excellent sensitive CEST effect for monitoring drug accumulation (at about 0.5 ppm) in tumor areas. The CEST signal of post-injection 2 h was significantly higher than that of pre-injection (2.17 ± 0.88% vs. 0. 09 ± 0.75%, p < 0.01). CONCLUSIONS: The nanomedicine with CEST imaging reflects the characterization of tumors and therapeutic functions has great potential medical applications.

NIR-Triggered Multifunctional and Degradable Nanoplatform Based on an ROS-Sensitive Block Copolymer for Imaging-Guided Chemo-Phototherapy.

Imaging-guided chemo-phototherapy based on multifunctional nanocarriers has emerged as a promising and high-efficient cancer treatment because of the inevitable limitations of single therapy. Herein, a near-infrared (NIR) light-activated degradable polymeric nanoplatform was fabricated for chemo-phototherapy. An NIR photosensitizer, IR780, and a chemotherapeutic drug, doxorubicin (DOX), were efficiently coloaded within a reactive oxygen species (ROS)-sensitive polymeric micelle based on an amphiphilic copolymer with degradable thioketal (TK) linkages. The obtained spherical nanoparticles (denoted as (IR780/DOX)@PTK) exhibited a notable photodynamic and photothermal effect upon NIR light exposure. Furthermore, due to the rapid cleavage of TK linkers induced by ROS generated from NIR-activated IR780, (IR780/DOX)@PTK also showed an NIR light-induced degradable feature, which can be used for light-triggered tumor-specific drug release and lead to ignorable systematic toxicity after biodegradation and drug delivery. Under the guidance of NIR fluorescence and photothermal dual modal imaging, (IR780/DOX)@PTK exhibited excellent tumor accumulation after intravenously injection into 4T1-tumor-bearing mice. As verified in both in vitro and in vivo study, (IR780/DOX)@PTK presented a significant tumor suppression effect by synergistic chemo-phototherapy.

NIR-Activated "OFF/ON" Photodynamic Therapy by a Hybrid Nanoplatform with Upper Critical Solution Temperature Block Copolymers and Gold Nanorods.

Photodynamic therapy (PDT) is a promising treatment modality for cancer treatment owing to its minimally invasive nature and negligible drug resistance. However, the disadvantages of conventional photosensitizers including universal aggregation-caused quenching (ACQ) effect or nonselective activation are still major hurdles for PDT clinical application. Herein, a new strategy for flexible manipulating photosensitizers in effective quenching and quick recovery of photoactivation is presented by introducing porphyrin units into upper critical solution temperature (UCST) block copolymer decorated gold nanorods (AuNR-P(AAm-co-AN-co-TPP)-b-PEG). The UCST block copolymer can achieve a self-quenching effect to make the porphyrin photosensitizers in the "Off" state by π-π stacking and hydrogen bonding interactions at physiological temperature, which greatly minimizes the nonselective phototoxicity of the photosensitizers to meet the requirement of phototherapy protected from sunlight. After the immigration of AuNR-P(AAm-co-AN-co-TPP)-b-PEG nanoparticles into the tumor tissue and the internalization by cancer cells, the UCST polymer chains can be extended under the local heating of AuNRs by NIR light irradiation, and then porphyrin photosensitizers are turned "On" to dramatically boost the PDT efficiency. Therefore, the process of PDT could be well manipulated in the "Off/On" state by the hybrid nanoplatform with UCST block copolymers and AuNRs, which will open new horizons for clinical treatments of PDT.