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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.

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Premature and incomplete drug release is the typical bottleneck of drug release in traditional chemotherapy. Synergistic therapies are highly desirable in medicine and biology because they can compensate for the drawbacks of single therapy and significantly enhance the therapeutic efficacy. Herein, a novel near infrared (NIR)-activated polymeric nanoplatform with upper critical solution temperature (UCST) was constructed for imageguided synergistic photothermal therapy (PTT) and chemotherapy. UCST-responsive amphiphilic block copolymers were synthesized by reversible addition−fragmentation chain-transfer (RAFT) polymerization and then co-assembled with IR780 and cabazitaxel (Cab) to form spherical nanoparticles (NPs). IR780/ Cab dual-loaded UCST polymeric NPs can produce local heating upon NIR laser irradiation and further lead to the dissociation of cargo-loaded NPs and controlled release of Cab. IR780 plays the role of both a heating generator and an activator for "ondemand" drug release. The investigation of in vivo fluorescence and photothermal imaging clearly demonstrated tumor targeting. Notably, both in vitro and in vivo studies illustrated that the synergistic PTT and chemotherapy presented better anticancer efficacy than that of PTT and chemotherapy simplely combined. Thus, the well-defined polymeric nanoplatform opens a versatile and effective path to develop image-guided synergistic therapies for tumor treatment.

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.