Folate-engineered chitosan nanoparticles: next-generation anticancer nanocarriers

Our plain-English summary of Folate-engineered chitosan nanoparticles: next-generation anticancer nanocarriers, by P. Kesharwani, K. Halwai, S.K. Jha, et al (Molecular Cancer, 2024).

The study

• Authors: P. Kesharwani, K. Halwai, S.K. Jha, M.H. Al Mughram, S.S. Almujri, W.H. Almalki, A. Sahebkar
• Journal: Molecular Cancer
• Published: 2024;23(1):244
• Type of article: Review
• Cited by: 67 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Chitosan nanoparticles (NPs) are well-recognized as promising vehicles for delivering anticancer drugs due to their distinctive characteristics. They have the potential to enclose hydrophobic anticancer molecules, thereby enhancing their solubilities, permeabilities, and bioavailabilities; without the use of surfactant, i.e., through surfactant-free solubilization. This allows for higher drug concentrations at the tumor sites, prevents excessive toxicity imparted by surfactants, and could circumvent drug resistance. Moreover, biomedical engineers and formulation scientists can also fabricate chitosan NPs to slowly release anticancer agents. This keeps the drugs at the tumor site longer, makes therapy more effective, and lowers the frequency of dosing. Notably, some types of cancer cells (fallopian tube, epithelial tumors of the ovary, and primary peritoneum; lung, kidney, ependymal brain, uterus, breast, colon, and malignant pleural mesothelioma) have overexpression of folate receptors (FRs) on their outer surface, which lets folate-drug conjugate-incorporated NPs to target and kill them more effectively. Strikingly, there is evidence suggesting that the excessively produced FR&αgr (isoforms of the FR) stays consistent throughout treatment in ovarian and endometrial cancer, indicating resistance to conventional treatment; and in this regard, folate-anchored chitosan NPs can overcome it and improve the therapeutic outcomes. Interestingly, overly expressed FRs are present only in certain tumor types, which makes them a promising biomarker for predicting the effectiveness of FR-targeted therapy. On the other hand, the folate-modified chitosan NPs can also enhance the oral absorption of medicines, especially anticancer drugs, and pave the way for effective and long-term low-dose oral metronomic scheduling of poorly soluble and permeable drugs. In this review, we talked briefly about the techniques used to create, characterize, and tailor chitosan-based NPs; and delved deeper into the potential applications of folate-engineered chitosan NPs in treating various cancer types.

© 2024. The Author(s).

In plain English

This article was a narrative literature review, not an asbestos study, and it did not examine asbestos exposure. The authors reviewed how chitosan nanoparticles (tiny drug carriers made from chitosan, a material derived from chitin in crustacean shells) are made, tested, and fitted with folate (vitamin B9) so that they attach to folate receptors on cancer cells. Searching PubMed and Scopus, they gathered 65 publications on folate-modified chitosan nanoparticles in tumor targeting from 2010 to 2024. They found no clinical trials of these nanoparticles for treating cancer. Mesothelioma appeared only in the review's description of earlier research. Citing other studies, the authors wrote that folate receptor alpha is highly expressed in most ovarian, uterine and ependymal brain tumors and in malignant pleural mesotheliomas. The nanoparticle studies they summarized were grouped under other cancers: breast, lung, ovarian, prostate, cervical, colon and pancreatic. The authors noted that the US FDA allows chitosan as a biomaterial but not for therapeutic purposes. They concluded that these nanoparticles face severe restrictions that prevent broad commercial use, and that past research was mainly done in laboratory settings.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative literature review
• Who was studied: Published literature found through PubMed and Scopus. This included 65 publications from 2010 to 2024 on folate-modified chitosan nanoparticles in tumor targeting. The studies reviewed were mainly laboratory cell-line and animal experiments.
• Exposure: Not applicable. No asbestos or other environmental or occupational exposure was studied. The subject was folate-anchored chitosan nanoparticles carrying anticancer drugs.
• Main results:
  • Citing earlier research, the review stated that folate receptor alpha is highly expressed in most ovarian, uterine and ependymal brain tumors and in malignant pleural mesotheliomas. This is a description of other studies, not a finding of this review.
  • The authors' search found no clinical trials of folate-modified chitosan nanoparticles for treating cancer.
  • For folate-receptor-targeted approaches in general, the search found 76 articles listed as clinical studies or clinical trials (phases I, II and III).
  • The review reported that a large phase III study of farletuzumab, a folate-receptor-targeted antibody, combined with carboplatin and taxane in platinum-sensitive recurrent ovarian cancer did not improve progression-free survival compared with carboplatin and taxane alone.
  • The detailed summaries of nanoparticle studies were grouped by breast, lung, ovarian, prostate, cervical, colon and pancreatic cancer. None of these sections concerned mesothelioma.
  • The review stated that the US FDA has allowed chitosan as a biomaterial, but not for therapeutic purposes.
• The authors' conclusion: The authors concluded that folate-engineered chitosan nanoparticles have severe restrictions that prevent broad commercial use, and that more work is needed on their limitations and possible harmful effects.
• Limitations the authors state:
  • Past research has focused mainly on making and testing the materials in laboratory settings.
  • Folate receptor levels may vary between patients, so targeting efficiency may vary.
  • The long-term toxicity of the chemically modified nanoparticles still needs full study.
  • More studies in living organisms are needed to understand how chitosan breaks down, what it breaks down into, and whether those products are toxic.

Topics

Medical terms in this study, explained in our Lexicon: Peritoneum, Pleural Mesothelioma, Biomarker, Targeted Therapy.

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