Dual pH-Responsive Calcium Phosphate Nanoparticles Conjugated with Folate by CuAAC Click Chemistry for Targeted Gemcitabine Delivery to Cancer Cells
Thales R. Machado, Aileen Winter, Kateryna Loza, Kathrin Kostka, Valtencir Zucolotto, Matthias Epple
TL;DR
This paper describes a new method to deliver the chemotherapy drug gemcitabine using pH-sensitive calcium phosphate nanoparticles targeted to cancer cells.
Contribution
The novelty is the dual pH-responsive nanoparticle system with folate conjugation via CuAAC click chemistry for targeted drug delivery.
Findings
The nanoparticles showed pH-responsive release of gemcitabine in endolysosomes.
Folate conjugation increased uptake in folate receptor-positive cancer cells.
The system exhibited high cytotoxicity in cancer cells while sparing normal cells.
Abstract
Calcium phosphate nanoparticles (CaP NPs) are biocompatible carriers widely studied for drug delivery due to their pH-responsive degradation and controlled release properties. In this study, CaP NPs stabilized with carboxymethyl cellulose (CMC) and coated with a silica layer were designed for gemcitabine (GEM) loading and folate (FA) conjugation, targeting cancer cells overexpressing folate receptor alpha (FRα). GEM was covalently coupled to CMC via an amide bond before CaP precipitation, creating a prodrug system. The NPs exhibited dual pH-responsive release, in which CaP dissolution combined with polymer-drug cleavage through acid-catalyzed hydrolysis of CMC-GEM within endolysosomes ensured intracellular bioavailability of free GEM molecules. FA conjugation by strong covalent bonds via copper-catalyzed azide–alkyne cycloaddition (CuAAC) click reaction enhanced the uptake of CaP NPs in…
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
Click any figure to enlarge with its caption.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
Figure 12
Figure 13
Figure 14Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsNanoparticle-Based Drug Delivery · Graphene and Nanomaterials Applications · Nanoplatforms for cancer theranostics