Stimulus responsive nanogel with innate near IR fluorescent capability for drug delivery and bioimaging.
A brighter, non toxic and biocompatible optical imaging agent is one of the major quests of biomedical research. Here in, we report a photoluminescent comacromer [PEG-poly(propylene fumarate)-citric acid-glycine] and novel stimulus (pH) responsive nanogel endowed with excitation wavelength dependent fluorescence (EDF) for combined drug delivery and bioimaging applications. The comacromer when excited at different wavelengths in visible region from 400nm to 640nm exhibits fluorescent emissions from 510nm to 718nm in aqueous condition. It has high Stokes shift (120nm), fluorescent lifetime (7 nanoseconds) and quantum yield (50%). The nanogel, C-PLM-NG, prepared with this photoluminescent comacromer and N,N-dimethyl amino ethylmethacrylate (DMEMA) has spherical morphology with particle size around 100nm and 180nm at pH 7.4 (physiological) and 5.5 (intracellular acidic condition of cancer cells) respectively. The studies on fluorescence characteristics of C-PLM NG in aqueous condition reveal large red-shift with emissions from 523nm to 700nm for excitations from 460nm to 600nm ascertaining the EDF characteristics. Imaging the near IR emission with excitation at 535nm was accomplished using cut-off filters. The nanogel undergoes pH responsive swelling and releases around 50% doxorubicin (DOX) at pH 5.5 in comparison with 15% observed at pH 7.4. The studies on in vitro cytotoxicity with MTT assay and hemolysis revealed that the present nanogel is non-toxic. The DOX-loaded C-PLM-NG encapsulated in Hela cells induces lysis of cancer cells. The inherent EDF characteristics associated with C-PLM NG enable cellular imaging of Hela cells. The studies on biodistribution and clearance mechanism of C-PLM-NG from the body of mice reveal bioimaging capability and safety of the present nanogel. This is the first report on a polymeric nanogel with innate near IR emissions for bioimaging applications.
Sree Chitra Tirunal Institute for Medical Sciences and Technology, Polymer Science Division, BMT Wing, Thiruvananthapuram 695012, Kerala, India.
Vineeth M
VM
Vijayan
Sree Chitra Tirunal Institute for Medical Sciences and Technology, Division of In vivo models and Testing, BMT Wing, Thiruvananthapuram 695012, Kerala, India.
Sachin J
SJ
Shenoy
Sree Chitra Tirunal Institute for Medical Sciences and Technology, Polymer Science Division, BMT Wing, Thiruvananthapuram 695012, Kerala, India.
Sunita P
SP
Victor
Sree Chitra Tirunal Institute for Medical Sciences and Technology, Polymer Science Division, BMT Wing, Thiruvananthapuram 695012, Kerala, India. Electronic address: mjayabalan52@gmail.com.
Jayabalan
J
Muthu
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005453:Fluorescence; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007091:Image Processing, Computer-Assisted / Q000379:methods; D007259:Infrared Rays; D051379:Mice; D000080385:Nanogels; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D014018:Tissue Distribution; D051598:Whole Body Imaging
D004337:Drug Carriers; D000080385:Nanogels; D011108:Polymers; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D004317:Doxorubicin; D011094:Polyethyleneimine
Bioimaging; Excitation dependent fluorescence; Nanogel; Near IR