Enzymatically Transformable Polymersome-Based Nanotherapeutics to Eliminate Minimal Relapsable Cancer

Bibliographische Detailangaben
Veröffentlicht in:	Advanced materials (Deerfield Beach, Fla.). - 1998. - 33(2021), 49 vom: 01. Dez., Seite e2105254
1. Verfasser:	Li, Junjie (VerfasserIn)
Weitere Verfasser:	Ge, Zhishen, Toh, Kazuko, Liu, Xueying, Dirisala, Anjaneyulu, Ke, Wendong, Wen, Panyue, Zhou, Hang, Wang, Zheng, Xiao, Shiyan, Van Guyse, Joachim F R, Tockary, Theofilus A, Xie, Jinbing, Gonzalez-Carter, Daniel, Kinoh, Hiroaki, Uchida, Satoshi, Anraku, Yasutaka, Kataoka, Kazunori
Format:	Online-Aufsatz
Sprache:	English
Veröffentlicht:	2021
Zugriff auf das übergeordnete Werk:	Advanced materials (Deerfield Beach, Fla.)
Schlagworte:	Journal Article bioavailability and toxicity inflammatory microenvironment minimal residual diseases postsurgical wounds premetastatic niche stimuli-responsive nanotherapeutics Matrix Metalloproteinase Inhibitors Colchicine SML2Y3J35T

Beschreibung
Zusammenfassung:	© 2021 Wiley-VCH GmbH. Prevention of metastatic and local-regional recurrence of cancer after surgery remains difficult. Targeting postsurgical premetastatic niche and microresiduals presents an excellent prospective opportunity but is often challenged by poor therapeutic delivery into minimal residual tumors. Here, an enzymatically transformable polymer-based nanotherapeutic approach is presented that exploits matrix metalloproteinase (MMP) overactivation in tumor-associated tissues to guide the codelivery of colchicine (microtubule-disrupting and anti-inflammatory agent) and marimastat (MMP inhibitor). The dePEGylation of polymersomes catalyzed by MMPs not only exposes the guanidine moiety to improve tissue/cell-targeting/retention to increase bioavailability, but also differentially releases marimastat and colchicine to engage their extracellular (MMPs) and intracellular (microtubules) targets of action, respectively. In primary tumors/overt metastases, the vasculature-specific targeting of nanotherapeutics can function synchronously with the enhanced permeability and retention effect to deter malignant progression of metastatic breast cancer. After the surgical removal of large primary tumors, nanotherapeutic agents are localized in the premetastatic niche and at the site of the postsurgical wound, disrupting the premetastatic microenvironment and eliminating microresiduals, which radically reduces metastatic and local-regional recurrence. The findings suggest that nanotherapeutics can safely widen the therapeutic window to resuscitate colchicine and MMP inhibitors for other inflammatory disorders
Beschreibung:	Date Completed 23.05.2022 Date Revised 31.05.2022 published: Print-Electronic Citation Status MEDLINE
ISSN:	1521-4095
DOI:	10.1002/adma.202105254