Novel antitumor system based on the targeting photothermal and pH-responsive nanocarriers, gold nanoshells coated oleanolic acid liposomes mediating by chitosan (GNOLs), is designed and synthesized for the first time. The GNOLs present spherical and uniform size (172.03 nm) with zeta potential (20.7 ± 0.4 mV), which are more easily accumulated in tumor. Meanwhile, the GNOLs exhibit a slow and controlled release of oleanolic acid at pH 7.4, as well as a rapid release at pH 5.5, which is beneficial for tumor-targeting drug release. Under near infrared (NIR) irradiation, hyperthermia can be generated by activated gold nanoshells to perform photothermal therapy effect, which triggers drug release from the carriers by activating the gel to liquid crystalline phase transition of the liposomes. Moreover, the NIR assisting drug release can be easily and selectively activated locally due to the spatially and real-timely controllable property of light. The experimental results also verify that the GNOLs with NIR irradiation achieve more ideal antitumor effects than other oleanolic acid formulations in vitro and in vivo. Hence, the drug delivery system exhibits a great potential in chemo-photothermal antitumor therapy.

Stimuli-responsive drug delivery and release have a great significance in cancer therapy.

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Hybrid liposome/metal nanoparticles are promising candidate drug-carriers for therapy of various diseases due to their unique photothermal effect. In this study, self-crystallized gold nanoparticles (Au NPs) and doxorubicin (DOX) were co-encapsulated within liposomes (Au/DOX-Lips) by thin film hydration and gel separation technology. The surface plasmon resonance bands of drug-carriers were controllable in the near-infrared (NIR) zone. When the complex liposome/metallic hybrids were irradiated by NIR light, they displayed higher endocytosis efficiency following the fracture of liposomal membranes and the release of Au NPs. Then, the Au NPs penetrated further into deeper tumor tissue to accomplish photothermal treatment. The Au/DOX-Lips showed an excellent antitumor effect, whose inhibition rate for tumor cells was up to 78.28%. In experiments on mice bearing tumors, the Au/DOX-Lips treated mice exhibited superior tumor suppression. This novel drug system provides huge potential for biomedical application.

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Chitosan modified OA liposomes can achieve the desired effect of tumor-targeting drug delivery and improve the anti-tumor efficacy.

Synergistic cancer therapy through the combination of chemotherapy with photothermal therapy has been gained more and more insights. Bimetallic nanostructures with near-infrared (NIR) plasmonic responses are considered prime candidates based on their superior photothermal conversion properties. Herein, novel poly branched Au–Pd bimetallic-nanoflowers-coated betulinic acid liposomes (BA-Lips@Pd@Au NFs) were designed and developed. The as-prepared BA-Lips@Pd@Au NFs with optimal size (144.4 nm) possessed good photostability under NIR-irradiation, high photothermal conversion efficiency (64.6%), and good biocompatibility. Moreover, the hyperthermia of drug delivery induced by NIR-irradiation dramatically improved the cell uptake of nanocapsules and enhanced the chemotherapeutic efficacy of tumor. Upon illumination by NIR light, the BA-Lips@Pd@Au NFs exhibited prominent synergetic effects of chemo-photothermal therapy with a tumor inhibition ratio (91.7%), which was higher than that of chemotherapy or photothermal therapy alone. Therefore, this rational design of nanocapsule with stimuli-responsive capability showed a versatile strategy to provide smart nanocapsule paradigms for cancer therapy.