Enhanced targeting of 3D pancreatic cancer spheroids by aptamer-conjugated polymeric micelles with deep tumor penetration.

Pancreatic cancer is a high degree malignant tumor which makes its diagnosis and treatment highly critical. The effect of conventional chemotherapy for pancreatic cancer is quite poor due to the low accumulation of the chemotherapeutic drugs at the tumor site. Therefore, enhancing the targeting efficiency and accumulation of the drug carrier at tumor site with subsequent release of drug within the effective time period is one of the key factors for successful targeted chemotherapy of pancreatic cancer. Our previous studies have demonstrated that aptamer can be a valid targeting moiety to guide the chemotherapeutic drug doxorubicin (DOX) to accumulate at the tumor tissue. Herein, the present study aims to further investigate the targeting efficiency as well as therapeutic efficacy of the drug delivery system comprised of aptamer-modified polymeric nano drug carrier encapsulated with DOX (DOX@PCL-b-PEO-Aptamer micelles). The in vitro cytotoxicity studies and laser confocal microscopy indicated that DOX@PCL-b-PEO-Aptamer micelles exhibited enhanced targeting and cytotoxic efficacy towards human pancreatic cancer cells (Panc-1 cells) as compared to free DOX and DOX-loaded PCL-b-PEO-NH2 micelles (DOX@PCL-b-PEO-NH2 micelles). Furthermore, the aptamer-decorated drug delivery system exhibited better tumor penetration into the three-dimensional (3D) spheroid of Panc-1 cells with successful release of DOX as compared to the drug delivery system without aptamer modification. Overall, this study suggests that the aptamer-modified polymeric micelles could be effectively employed for the targeted delivery of anticancer drug to treat pancreatic cancer in near future.