Abstract
A combination of chemo- and photo-thermal therapy (PTT) has provided a promising efficient approach for cancer therapy. To achieve the superior synergistic chemotherapeutic effect with PTT, the development of a simple theranostic nanoplatform that can provide both cancer imaging and a spatial-temporal synchronism of both therapeutic approaches are highly desired. Our previous study has demonstrated that near-infrared (NIR) light-triggered biodegradable chitosan-based amphiphilic block copolymer micelles (SNSC) containing light-sensitive 2-nitrobenzyl alcohol and NIR dye cypate on the hydrophobic block could be used for fast light-triggered drug release. In this study, we conjugated the SNSC micelles with tumor targeting ligand c(RGDyK) and also encapsulated antitumor drug Paclitaxel (PTX). The results show that c(RGDyK)-modified micelles could enhance the targeting and residence time in tumor site, as well as be capable performing high temperature response for PTT on cancer cells and two-photon photolysis for fast release of anticancer drugs under NIR irradiation. In vitro release profiles show a significant controlled release effort that the release concentration of PTX from micelles was significantly increased with the exposure of NIR light. In vitro and in vivo antitumor studies demonstrate that, compared with chemo or PTT treatment alone, the combined treatment with the local exposure of NIR light exhibited significantly enhanced anti-tumor efficiency. These findings indicate that this system exhibited great potential in tumor-targeting imaging and synchronous chemo- and photo-thermal therapy.
Highlights
Multifunctional nanomaterials, where therapeutic and imaging features are integrated within a single nanoplatform, has offered a promising opportunity for concurrent diagnosis and treatment of cancer tumors [1,2,3]
Survival rates of mice in the SNSC-cypate-PTX with or without NIR irradiation and non-NIR irradiation c(RGDyK)-SNSC-cypatePTX treated group reach to 75%, 88% and 88%. These results further demonstrated the low cytotoxicity of PTX after encapsulated into micelles and indicated that after irradiation, combinatorial photo-thermal therapy (PTT) and chemotherapy based on c(RGDyK)-SNSC-cypate-PTX can effectively improve the survival quality of mice and prolong their lifetime
We developed NIR lighttriggered micelles that could simultaneously deliver anticancer drug PTX and NIR dye cypate to tumor sites for combined chemo-photothermal therapy
Summary
Multifunctional nanomaterials, where therapeutic and imaging features are integrated within a single nanoplatform, has offered a promising opportunity for concurrent diagnosis and treatment of cancer tumors [1,2,3]. PTT destroys cancer cells with minimal invasiveness by generating the localized heat within a tumor site upon the absorption of specific light wavelength [8] Those near-infrared (NIR) resonant nanomaterials are chosen due to the optimal transmission to tissue in the NIR region. Some studies have shown that PTT alone will not destroy all malignant cells and may allow residual cells to survive after photo-thermal injury. To overcome this limitation, combined PTT with chemotherapy in a single platform is expected to generate a synergistic effect and decrease cancer recurrence rates [9,10,11,12,13]. The development of a simple theranostic nanoplatform that can provide both cancer imaging and a spatial-temporal synchronism of PTT and chemotherapy are highly desired
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