Abstract
Current limitations of cancer therapy include the lack of effective strategy for target delivery of chemotherapeutic drugs, and the difficulty of achieving significant efficacy by single treatment. Herein, we reported a synergistic chemo-photothermal strategy based on aptamer (Apt)-polydopamine (pD) functionalized CA-(PCL-ran-PLA) nanoparticles (NPs) for effective delivery of docetaxel (DTX) and enhanced therapeutic effect. The developed DTX-loaded Apt-pD-CA-(PCL-ran-PLA) NPs achieved promising advantages, such as (i) improved drug loading content (LC) and encapsulation efficiency (EE) initiated by star-shaped copolymer CA-(PCL-ran-PLA); (ii) effective target delivery of drugs to tumor sites by incorporating AS1411 aptamers; (iii) significant therapeutic efficacy caused by synergistic chemo-photothermal treatment. In addition, the pD coating strategy with simple procedures could address the contradiction between targeting modification and maintaining formerly excellent bio-properties. Therefore, with excellent bio-properties and simple preparation procedures, the DTX-loaded Apt-pD-CA-(PCL-ran-PLA) NPs effectively increased the local drug concentration in tumor sites, minimized side effects, and significantly eliminated tumors, indicating the promising application of these NPs for cancer therapy.
Highlights
Breast cancer, the leading type of cancer for deaths among women worldwide, has caused over an estimated 2,421,698 deaths for the year 2015 (Global Burden of Disease Cancer Collaboration, 2017)
As could be concluded from this figure, the survival time of “DTX/Apt-pD-colic acid (CA)-(PCL-ranPLA) NPs + NIR” group was at least extended by 35, 28, 14, and 11 days compared to “Saline” group, “Taxotere R ” group, “DTX/Apt-pD-CA-(PCL-ran-PLA) NPs” group, and “Apt-pDCA-(PCL-ran-PLA) NPs + NIR” group. These results further demonstrated the significant therapeutic efficacy of this target chemo-photothermal therapy strategy based on DTX/Apt-pDCA-(PCL-ran-PLA) NPs, indicating these NPs are able to be applied as promising targeting drug delivery systems for synergistic chemo-photothermal therapy of breast cancer
We for the first time reported the successful synthesis of robust DTX/Apt-pD-CA-(PCL-ran-PLA) NPs with star shaped CA-(PCL-ran-PLA) copolymers, which could be applied as promising targeting drug delivery systems for synergistic chemo-photothermal therapy of breast cancer
Summary
The leading type of cancer for deaths among women worldwide, has caused over an estimated 2,421,698 deaths for the year 2015 (Global Burden of Disease Cancer Collaboration, 2017). The key to solve the side effects caused by cytotoxic anticancer drugs is to increase the local effective drug concentrations in the tumor sites, which could be addressed by employing polymeric nanoparticles (NPs) as highly promising target drug delivery systems (Kamaly et al, 2016; Kakkar et al, 2017; Nie et al, 2017; Tao et al, 2017c; Xu et al, 2017). By combining two or more therapies with different therapeutic mechanisms in one nano-system (e.g., chemotherapy and photothermal therapy), a promising strategy could be achieved to significantly enhance the therapeutic efficacy and have a better long-term prognosis (Cheng et al, 2017; Tao et al, 2017d). Developing multifunctional target delivery platforms that intelligently integrated with different therapeutic approaches is urgently needed for effective cancer therapy
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