Cu_2–<i>x</i>S Nanocrystals Cross-Linked with Chlorin e6-Functionalized Polyethylenimine for Synergistic Photodynamic and Photothermal Therapy of Cancer

Achieving an integrated system for combinational therapy of cancer with enhanced efficacy is always a challenge. A multifunctional system (CCeT nanoparticles (NPs)) for a synergistic photodynamic and photothermal cancer therapy was successfully developed. This system is composed of Cu_2–<i>x</i>S nanoclusters functionalized with chlorin e6 (Ce6)-conjugated branched polyethylenimine (PEI-Ce6) and mitochondria-targeting 3-(carboxypropyl)­triphenylphosphonium bromide (TPP-COOH). The colocalization of the resulted CCeT NPs inside the mitochondria of cancer cells was proven. The CCeT NPs exhibited significant photodynamic therapy (PDT) efficacy due to efficient singlet oxygen (¹O₂) generation triggered by a 630 nm laser. This system also showed excellent photothermal conversion capability upon the irradiation of 808 nm laser for photothermal therapy (PTT). In particular, the platform achieved nearly 100% inhibitory rate of the tumor growth in vivo through combinational PDT and PTT. Thus, the CCeT NPs could efficiently inhibit the tumor growth in vitro and in vivo by combinational PDT and PTT, offering synergistic therapeutic efficiency as compared to PTT or PDT alone

Combined Photodynamic and Photothermal Therapy Using Cross-Linked Polyphosphazene Nanospheres Decorated with Gold Nanoparticles

A rational combination of photodynamic therapy (PDT) and photothermal therapy (PTT) could achieve a synergistic therapeutic effect to enhance therapeutic efficacy in the cancer treatment. Herein, polyphosphazene nanospheres as a novel kind of photosensitizer carriers were synthesized by anchoring and isolating photosensitizing porphyrin monomers covalently in the cross-linked structure. Gold nanoparticles were then immobilized on the surface of the nanospheres to introduce the photothermal performance. The hybrid system was eventually conjugated by polyethylene glycol to decrease its cytotoxicity. The morphology analysis showed that the nanospheres were covered by homogeneously dispersed gold nanoparticles. In this way, the resulted system could afford efficient photodynamic and photothermal effect simultaneously, as confirmed by the cancer cell killing studies. The cell experiments demonstrated that the as-prepared polyphosphazene nanospheres with inherent fluorescence could be internalized by HeLa cells, showing high performance of combined PDT and PTT under suitable light irradiation. Thus, this integrated system presents its effectiveness to achieve combined PDT and PTT for enhanced cancer therapeutics

Theranostic Prodrug Vesicles for Imaging Guided Codelivery of Camptothecin and siRNA in Synergetic Cancer Therapy

The construction of prodrugs has been a popular strategy to overcome the limitations of chemotherapeutic drugs. However, complicated synthesis procedures and laborious purification steps make the fabrication of amphiphilic prodrugs rather difficult. By harnessing the concept of host–guest interaction, we designed and prepared a supra-amphiphile consisting of a dendritic cyclodextrin host and an adamantane/naphthalimide-modified camptothecin guest through glutathione-responsive disulfide linkage. This host–guest complex could self-assemble in aqueous solution to give nanosized vesicles. When the disulfide bond in adamantane/naphthalimide-modified camptothecin was cleaved by glutathione, the fluorescence of the freed adamantane/naphthalimide unit showed a significant red shift with enhanced intensity. Such glutathione-responsive fluorescence change allows for intracellular imaging and simultaneous monitoring of drug release in real time. On account of abundant positively charged amine groups on the supramolecular vesicle surface, siRNA (siPlK1) could be efficiently loaded on the vesicle. The gel retardation and fluorescence experiments proved that the siPlK1 was successfully bonded to the supramolecular vesicle. The vesicle with dendritic cyclodextrin ring exhibited negligible cytotoxicity even at high concentrations, avoiding the shortcoming of cytotoxicity from commonly used gene vectors. In vitro studies demonstrated that the loaded siRNA was transported into cancer cells to improve cancer therapeutic efficacy. Thus, we developed a prodrug-based supramolecular amphiphile via the host–guest interaction with better therapeutic performance than free camptothecin. The assembled system was utilized as a drug/gene vector to achieve combinational gene therapy and chemotherapy with a synergistic effect, providing an alternative strategy to deliver both prodrug and therapeutic gene