[Development of Tumor-targeting Antitumor Agents Based on Polymer Effect]

Area of Science:

• Polymer Chemistry
• Nanomedicine
• Oncology

Background:

• Solid tumors exhibit the enhanced permeability and retention (EPR) effect, allowing for passive accumulation of nanoparticles.
• Traditional chemotherapy faces challenges with tumor selectivity and systemic toxicity.

Purpose of the Study:

• To develop polymer-drug conjugates for tumor-selective delivery of photosensitizing and antitumor agents.
• To leverage the EPR effect and polymer properties for improved cancer treatment.

Main Methods:

• Conjugation of zinc-protoporphyrin IX (ZnPP) to an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer (P-ZnPP) for photosensitization.
• Development of a pirarubicin (THP) HPMA copolymer conjugate (P-THP) via a hydrazone bond for chemotherapy.
• Evaluation of EPR-dependent accumulation, tumor penetration, and antitumor activity in tumor models.

Main Results:

• P-ZnPP enhanced tumor distribution and enabled fluorescence visualization.
• P-THP demonstrated EPR-dependent accumulation and tumor-selective THP release, leading to potent antitumor activity.
• Higher molecular weight P-THP derivatives (DP-THP, SP-THP) exhibited superior efficacy.
• P-THP showed effectiveness in both implanted and autochthonous tumor models.

Conclusions:

• HPMA-based polymer-drug conjugates offer a promising strategy for tumor-selective drug delivery.
• Nanomedicines utilizing the polymer effect and EPR effect hold potential for clinical cancer therapeutics.