Stimuli-Responsive Covalent Organic Frameworks for Cancer Therapy.

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Abstract

Chemotherapy as a common anticancer therapeutic modality is often challenged by various obstacles such as poor stability, low solubility, and severe side effects of chemotherapeutic agents as well as multidrug resistance of cancerous cells. Nanoparticles in the role of carriers for chemotherapeutic drugs and platforms for combining different therapeutic approaches have effectively participated in overcoming such drawbacks. In particular, nanoparticles able to induce their therapeutic effect in response to specific stimuli like tumor microenvironment characteristics (e.g., hypoxia, acidic pH, high levels of glutathione, and overexpressed hydrogen peroxide) or extrinsic stimulus of laser light bring about more precise and selective treatments. Among them, nanostructures of covalent organic frameworks (COFs) have drawn great interest in biomedical fields during recent years. Possessing large surface area, high porosity, structural stability, and customizable architecture, these biocompatible porous crystalline polymers properly translate to promising platforms for drug delivery and induction of combination therapies. With the focus on stimuli-responsive characteristics of nanoscale COFs, this study aims to propose an overview of their potentiality in cancer treatment on the basis of chemotherapy alone or in combination with sonodynamic, chemodynamic, photodynamic, and photothermal therapies.

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Covalent organic frameworks (COFs) have been designed and successfully synthesized by condensation reactions of phenyl diboronic acid {C6H4[B(OH)2]2} and hexahydroxytriphenylene [C18H6(OH)6]. Powder x-ray diffraction studies of the highly crystalline products (C3H2BO)6.(C9H12)1 (COF-1) and C9H4BO2 (COF-5) revealed expanded porous graphitic layers that are either staggered (COF-1, P6(3)/mmc) or eclipsed (COF-5, P6/mmm). Their crystal structures are entirely held by strong bonds between B, C, and O atoms to form rigid porous architectures with pore sizes ranging from 7 to 27 angstroms. COF-1 and COF-5 exhibit high thermal stability (to temperatures up to 500 degrees to 600 degrees C), permanent porosity, and high surface areas (711 and 1590 square meters per gram, respectively).

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Elvin Blanco, Haifa Shen, Mauro Ferrari (2015)

Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.

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The intrinsic limits of conventional cancer therapies prompted the development and application of various nanotechnologies for more effective and safer cancer treatment, herein referred to as cancer nanomedicine. Considerable technological success has been achieved in this field, but the main obstacles to nanomedicine becoming a

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Author and article information

Journal

Journal ID (iso-abbrev): ACS Appl Mater Interfaces

Title: ACS applied materials & interfaces

Publisher: American Chemical Society (ACS)

ISSN (Electronic): 1944-8252

ISSN (Print): 1944-8244

Publication date (Electronic): Oct 02 2024

Volume: 16

Issue: 39

Affiliations

[1 ] Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 91388-13944, Iran.

[2 ] Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 91388-13944, Iran.

[3 ] Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 91388-13944, Iran.

[4 ] Department of Chemistry, University of Quebec at Montreal, Montreal, Quebec H3C 3P8, Canada.

Article

DOI: 10.1021/acsami.4c07040

PubMed ID: 39163539

SO-VID: 74dabcde-4f01-42f6-ae7d-5f29924816fb

History

Keywords: combination therapy,covalent organic frameworks,drug delivery,stimuli-responsive,cancer therapy

Data availability:

Keywords: combination therapy, covalent organic frameworks, drug delivery, stimuli-responsive, cancer therapy

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