Enhanced photothermal and chemotherapy of pancreatic tumors by degrading the extracellular matrix

The degradation of extracellular matrix (ECM) to increase drug permeability is an attractive approach to enhancing pancreatic cancer therapy efficiency. Herein, polypyrrole nanoparticles (PPy NPs) were prepared by a template-guided chemical oxidation method. These PPy NPs with abundant surface pores were used to load the anticancer drug doxorubicin (DOX). In order to intelligently control the DOX release, PPy/DOX NPs were further entrapped with a thermoresponsive ligand, lauric acid (LA), to form PPy-LA/DOX NPs. Bromelain (BL) was then grafted onto the surface of PPy-LA NPs or PPy-LA/DOX NPs through an amidation reaction with the carboxyl group of LA. It was found that the DOX release of PPy-LA/DOX NPs was pH and temperature responsive, reaching a maximum amount of 85.9% within 48 h at pH = 5.4 and 50 degrees C. Moreover, it was demonstrated that the resultant PLB (PPy-LA-BL) NPs could efficiently hydrolyze the collagen in ECM and enhance the permeability of DOX to the pancreatic tumor. Remarkably, PLB NPs not only featured admirable photothermal conversion but also exhibited obvious photoacoustic imaging capability, which enabled imaging-guided enhanced tumor abla-tion. This study is anticipated to provide a feasible strategy to improve the permeability of nanoparticles to tumors.

Automated summary

This study demonstrates a feasible strategy to enhance the permeability of nanoparticles to pancreatic tumors. By synthesizing polypyrrole nanoparticles (PPy NPs) and loading the anticancer drug doxorubicin (DOX) within them, the release of DOX is intelligently controlled using a thermoresponsive ligand lauric acid (LA). The grafting of bromelain (BL) onto the surface of PPy-LA NPs or PPy-LA/DOX NPs enhances the permeability of DOX to pancreatic tumors. Moreover, the resulting PLB NPs also exhibit photothermal conversion and photoacoustic imaging capabilities, enabling imaging-guided tumor ablation.