title: Carbon dots incorporated polymeric hydrogels as multifunctional platform for imaging and induction of apoptosis in lung cancer cells.
abstract: Multifunctional hydrogels offer a seemingly efficient system for delivery of drugs and bioimaging modalities. The present study deals with the facile development of chitosan-based hydrogel formulation composed of highly fluorescent carbon dots (CDs) and loaded with a model anticancer drug, 5-Fluorouracil (5-FU). Herein, CDs were embedded firmly within the hydrogel matrices (CD-HY) via non-covalent interactions during the ionic cross-linking reaction. Furthermore, these hydrogels could effectively encapsulate 5-FU through hydrophobic interactions to form 5-FU@CD-HY. In this way, it was possible to combine the merits of both CDs and 5-FU on a common platform for monitoring the cellular uptake as well as therapeutic effects. Field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) illustrated the porous nature and formation of 5-FU@CD-HY. Besides, functional characteristics of 5-FU@CD-HY such as surface area, mechanical strength, swelling behavior and drug release were investigated. In vitro studies revealed the multifunctional aspects of 5-FU@CD-HY in monitoring the cellular uptake and inflicting apoptosis in A549 cells. Green fluorescence of CDs in 5-FU@CD-HY aided the qualitative and quantitative assessment of cellular uptake. In addition to this, the fluorescence of CDs could be used to detect apoptosis instigated by 5-FU, eliminating the need for multiplex dyes. Induction of apoptosis in 5-FU@CD-HY treated cells was evidenced by changes in cell cycle distributions and visualization of characteristic apoptotic bodies through FE-SEM. Apoptotic gene expression studies further elucidate the molecular mechanism involved in eliciting apoptosis. Thus, hydrogels mediated integration of fluorescent CDs with chemotherapeutic agents provides a new dimension for the potential use of hydrogels in cancer theranostics.
authors: Nanobiotechnology Laboratory, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.
authors: Abhay
authors: A
authors: Sachdev
authors: Nanobiotechnology Laboratory, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India.
authors: Ishita
authors: I
authors: Matai
authors: Nanobiotechnology Laboratory, Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India; Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand 247667, India. Electronic address: pgopifnt@iitr.ernet.in.
authors: P
authors: P
authors: Gopinath
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D002244:Carbon / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D065546:Drug Liberation; D005472:Fluorouracil / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D011108:Polymers / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013053:Spectrophotometry
chemical_list: D000964:Antimetabolites, Antineoplastic; D051017:Apoptosis Regulatory Proteins; D020100:Hydrogels; D011108:Polymers; D002244:Carbon; D005472:Fluorouracil
keywords: 5-Fluorouracil; Apoptosis; Carbon dots; Hydrogel; Theranostics