Enzyme-Enhanced Codelivery of Doxorubicin and Bcl-2 Inhibitor by Electrospun Nanofibers for Synergistic Inhibition of Prostate Cancer Recurrence

Abstract

One of the great challenges of postoperative prostate cancer management is tumor recurrence. Although postoperative chemotherapy presents benefits to inhibit unexpected recurrence, it is still limited due to the drug resistance or intolerable complications of some patients. Electrospun nanofiber, as a promising drug carrier, demonstrating sustained drug release behavior, can be implanted into the tumor resection site during surgery and is conductive to tumor inhibition. Herein, we fabricated electrospun nanofibers loaded with doxorubicin (DOX) and ABT199 to synergistically prevent postoperative tumor recurrence. Enzymatic degradation of the biodegradable electrospun nanofibers facilitated the release of the two drugs. The primarily released DOX from the electrospun nanofibers effectively inhibited tumor recurrence. However, the sustained release of DOX led to drug resistance of the tumor cells, yielding unsatisfactory eradication of the residual tumor. Remarkably, the combined administration of DOX and ABT199, simultaneously released from the nanofibers, not only prolonged the chemotherapy by DOX but also overcame the drug resistance via inhibiting the Bcl-2 activation and thereby enhancing the apoptosis of tumor cells by ABT199. This dual-drug-loaded implant system, combining efficient chemotherapy and anti-drug resistance, offers a prospective strategy for the potent inhibition of postoperative tumor recurrence.

Advanced applications of smart electrospun nanofibers in cancer therapy: With insight into material capabilities and electrospinning parameters

“…In order to address the issue of treatment resistance, the simultaneous release of ABT199, a Bcl-2 inhibitor, from the nanofibers was employed. This resulted in the deactivation of the Bcl-2 protein and consequently increased the apoptosis of tumor cells that are resistant to drugs ( Liu et al, 2022c ). Also, some researchers have designed nanofibers that release their drug at a certain period of time.…”

“…17 Graphical representation of (a) the production of DOX-ABT199@Fibers, (b) the process of preventing tumor recurrence, and (c, d) the local drug delivery following tumor resection and the combined impact of the Bcl-2 inhibitor ABT199 and the sustainedly released DOX (the red cross indicates that a process was undermined). Reprinted from ( Liu et al, 2022c ), copyright 2022 with permission from MDPI. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)…”

[12]aneN3-modified camptothecin and PEGylated AIEgens co-assembly into core–shell nanoparticles with ROS/NTR dual-response for enhanced cancer therapy

“…Recently, there have been notable advances in cancer therapy through the co-delivery of anticancer drugs and genes, which have achieved synergistic therapeutic effects. 27–31 A variety of nano-carriers has been used to deliver chemotherapeutic agents and genes. Typically, the hydrophobic chemotherapeutic agent is entrapped within self-assembled NPs through non-covalent interactions, 32 while the gene is complexed with cationic motifs of the nano-carrier via electrostatic condensation.…”

Targeting Adhesive Tumor Adventitia via Injectable Electrospun Short Fibers in Perfusion of Intraperitoneal Sporadic Tumors

“…So far, electrospun fiber has been utilized mainly in the form of a membrane, but sporadic tumors spread widely, so it was hard to use the electrospun fiber membrane as a local therapy. [ 36,37 ]…”

“…So far, electrospun fiber has been utilized mainly in the form of a membrane, but sporadic tumors spread widely, so it was hard to use the electrospun fiber membrane as a local therapy. [36,37] In this research, inspired by intraperitoneal chemotherapy, by means of mussel-stimulated polydopamine (PDA) coating and folate acid (FA) modification, we designed the injectable PTXloaded FA-modified electrospun short fibers (FA-IESF@PTX) with both targeted adhesiveness and long-term penetration functions. [38,39] With a simple injection to achieve the goal that short fibers targeted adhere to tumors and slowly release drugs into tumors, we found FA-IESF@PTX an effective material to promote the situation of trauma, low penetration efficiency, low tumor-targeting ability, and poor repeatability.…”