Efficient penetration and retention of therapeutic agents in tumor tissues can be realized through rational design of drug delivery systems. Herein, a polymer-dendron conjugate, POEGMA-b-p(GFLG-Dendron-Ppa) (GFLG-DP), is presented, which allows a cathepsin-B-triggered stealthy-to-sticky structural transformation. The compositions and ratios are optimized through dissipative particle dynamics simulations. GFLG-DP displays tumor-specific transformation and the consequently released dendron-Ppa is found to effectively accumulate on the tumor cell membrane. The interaction between the dendron-Ppa and the tumor cell membrane results in intracellular and intercellular transport via membrane flow, thus achieving efficient deep penetration and prolonged retention of therapeutic agents in the solid tumor tissues. Meanwhile, the interaction of dendron-Ppa with the endoplasmic reticulum disrupts cell homeostasis, making tumor cells more vulnerable and susceptible to photodynamic therapy. This platform represents a versatile approach to augmenting the tumor therapeutic efficacy of a nanomedicine via manipulation of its interactions with tumor membrane systems.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/adma.202200048 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Enzyme-triggered deep tumor penetration of a dual-drug nanomedicine enables an enhanced cancer combination therapy.
Bioact Mater
August 2023
Huaxi MR Research Center (HMRRC), Department of Radiology, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Cancer cells could be eradicated by promoting generation of excessive intracellular reactive oxygen species (ROS) via emerging nanomedicines. However, tumor heterogeneity and poor penetration of nanomedicines often lead to diverse levels of ROS production in the tumor site, and ROS at a low level promote tumor cell growth, thus diminishing the therapeutic effect of these nanomedicines. Herein, we construct an amphiphilic and block polymer-dendron conjugate-derived nanomedicine (Lap@pOEGMA-b-p(GFLG-Dendron-Ppa), GFLG-DP/Lap NPs) that incorporates a photosensitizer, Pyropheophorbide a (Ppa), for ROS therapy and Lapatinib (Lap) for molecular targeted therapy.
View Article and Find Full Text PDFA Transformable Amphiphilic and Block Polymer-Dendron Conjugate for Enhanced Tumor Penetration and Retention with Cellular Homeostasis Perturbation via Membrane Flow.
Adv Mater
April 2022
Huaxi MR Research Center (HMRRC), Animal Experimental Center, Department of Radiology, National Clinical Research Center for Geriatrics, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.
Efficient penetration and retention of therapeutic agents in tumor tissues can be realized through rational design of drug delivery systems. Herein, a polymer-dendron conjugate, POEGMA-b-p(GFLG-Dendron-Ppa) (GFLG-DP), is presented, which allows a cathepsin-B-triggered stealthy-to-sticky structural transformation. The compositions and ratios are optimized through dissipative particle dynamics simulations.
View Article and Find Full Text PDFTrastuzumab targeted micellar delivery of docetaxel using dendron-polymer conjugates.
Biomater Sci
May 2020
Department of Chemistry, Bogazici University, Istanbul, 34342, Turkey. and Center for Life Sciences and Technologies, Bogazici University, Istanbul, 34342, Turkey.
Incorporation of a therapeutic antibody into nanosized drug delivery systems can improve their target specificity. This work reports an antibody-conjugated targeted delivery system composed of polymer-dendron conjugates. Trastuzumab is chosen as the targeting moiety, since it is clinically used against tumor cells expressing HER2 receptors.
View Article and Find Full Text PDFDesigning Dendron-Polymer Conjugate Based Targeted Drug Delivery Platforms with a "Mix-and-Match" Modularity.
Bioconjug Chem
December 2017
Department of Chemistry and ‡Center for Life Sciences and Technologies, Bogazici University, Istanbul, 34342, Turkey.
Polymeric micellar systems are emerging as a very important class of nanopharmaceuticals due to their ability to improve pharmacokinetics and biodistribution of chemotherapy drugs, as well as to reduce related systemic toxicities. While these nanosized delivery systems inherently benefit from passive targeting through the enhanced permeation and retention effect leading to increased accumulation in the tumor, additional active targeting can be achieved through surface modification of micelles with targeting groups specific for overexpressed receptors of tumor cells. In this project, nontoxic, biodegradable, and modularly tunable micellar delivery systems were generated using two types of dendron-polymer conjugates.
View Article and Find Full Text PDFEffects of molecular geometry on the self-assembly of giant polymer-dendron conjugates in condensed state.
Soft Matter
May 2014
Department of Polymer Science, College of Polymer Science and Polymer Engineering, The University of Akron, Akron, OH 44325-3909, USA.
A series of giant polymer-dendron conjugates with a dendron head and a linear polymer tail were synthesized via"click" chemistry between azide-functionalized polystyrene (PS(N), N: degree-of-polymerization) and t-butyl protected, alkyne-functionalized second generation dendron (tD), followed by a deprotection process to generate a dendron termini possessing nine carboxylic acid groups. The molecular structures were confirmed by nuclear magnetic resonance, size-exclusion chromatographic analyses, and matrix-assisted laser desorption ionization time-of-flight mass spectra. These well-defined conjugates can serve as a model system to study the effects of the molecular geometries on the self-assembly behaviour, as compared with their linear analogues.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!