Two fluorescent nanomedicines based on small molecular cyanine–platinum conjugates have been prepared via a nanoprecipitation method and characterized by transmission electron microscopy (TEM) as well as dynamic light scattering (DLS). The conjugates exhibited an enhanced fluorescence in their nanoparticle formulation compared to that in solution. The nanomedicines could be endocytosed by cancer cells as revealed by confocal laser scanning microscopy (CLSM) and showed high cellular proliferation inhibition. Fluorescent platinum nanomedicines prepared directly from small molecules could be an alternative strategy for developing new drugs with simultaneous cellular imaging and cancer therapy functions.

Nanomedicines assembled directly from drug molecules possess several advantages, including precise molecular structure and high content of drugs. Herein, porphyrin–paclitaxel conjugates (Py-s-s-PTX) were synthesized by using a disulfide bond as a linker. The Py-s-s-PTX could self-assemble into nanoparticles (Py-s-s-PTX NPs) with a size of about 100 nm via disulfide-induced assembly. Py-s-s-PTX NPs are highly stable under biological conditions and could be destroyed in the presence of reducing agents as revealed by dynamic light scattering. The obtained Py-s-s-PTX NPs could be internalized by cancer cells via endocytosis and disassociated in the reducing cytoplasm, thus releasing PTX in cancer cells. Endosomal escape triggered upon irradiation could enhance the cytotoxicity of paclitaxel, and Py-s-s-PTX NPs possess cytotoxicity comparable to that of free PTX. We believe that this disulfide-assembled nanomedicine represents a new and important development for chemotherapy in cancer therapy.

Combination therapy of paclitaxel (PTX) and cisplatin has been used to treat several cancers in clinic practice, but often causes serious systemic toxicity. Co-delivery of PTX and cisplatin by means of polymeric micelles can reduce the systemic toxicity, but often needs two carrier polymers because of the solubility difference between them. Therefore, a strategy is developed to co-deliver both PTX and cisplatin with only one carrier polymer by encapsulating PTX in the core of a polymeric micelle and cross-linking the micelle with cisplatin. The PTX and Pt contents in the micellar formulation M(PTX/Pt) were 10 and 14 wt %, respectively. In vitro cytotoxicity of M(PTX/Pt) was evaluated via 3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide assay in comparison with PTX and its micelle M(PTX), cisplatin and its micelle M(Pt), and PTX/cisplatin combination towards human hepatocarcinoma (SMMC-7721) cells and chemoresistant SMMC-7721(SMMC-7721R) cells. The M(PTX/Pt) exhibited a high synergistic effect in the inhibition of cell growth and proliferation of both SMMC-7721 and SMMC-7721R cells and showed reasonable drug-resistance relief. The synergistic effect and resistance relief were further supported or explained by intracellular uptake measurement of dye-labeled micelles and by the confocal laser scanning microscopy observation of SMMC-7721 and SMMC-7721R cells treated with various formulations. Therefore, M(PTX/Pt) micelles were expected to find potential application in cancer chemotherapy. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41440.

A series of four-arm star block copolymers poly(ethylene glycol)-block-poly(d,l-lactide) (PEG-PDLLA) with different hydrophobic length were synthesized by ring-opening polymerization of lactide and characterized using ¹H NMR and gel permeation chromatography (GPC). These copolymers could self-assemble in aqueous solution to form the vesicle structure with controlled size and morphologies. Transmission electron microscopy (TEM) and DLS show the polymersomes are spherical with diameter of 70∼500 nm. The polymersomes made by direct hydration of copolymer thin films in water exhibit the controllable ability of encapsulating hemoglobin under mild condition. The hemoglobin content in the polymersomes could reach to 35 wt %. More importantly, the encapsulated hemoglobin keeps its own bioactivity and is capable of binding oxygen. This hemoglobin-encapsulated four-arm PEG-PLA polymersomes could have the potential to be applied as an artificial oxygen carrier for transfusion. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40433.

Cisplatin was incorporated into polymeric carriers through the coordination of Pt with the carboxylic groups of methoxy-poly(ethylene glycol) (mPEG)-block-poly[(2-carboxy-ethylsulfanyl)-propyl glycidyl ether] (PCPGE). The mPEG-b-PCPGE/Pt complexes with a Pt content of 14 wt % could self-assemble into spheric micelles with diameter of about 80 nm in aqueous solution. The effective internalization of the polymer platinum micelles by the cells via an endocytosis mechanism was confirmed by confocal laser scanning microscopy and flow cytometry. The antitumor activity of the polymeric micelles was similar to that of cisplatin in vitro. The in vivo blood clearance of platinum was studied, and the results show that the micelles exhibited longer blood circulation than the free cisplatin. The biodistribution of cisplatin and its micelles in mice was studied through the measurement of the Pt content in plasma, organs, and tumors, especially in tumor cell DNA. Their antitumor activity in vivo, assessed in mice bearing H22 liver cancers, showed that the micelles exhibited greater antitumor efficacy than free cisplatin. Therefore, this polymer platinum micelle is a promising candidate as a smart antitumor drug carrier for malignancy therapy in future clinical applications. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40764.