Poly(Styrene-Co-Maleic Acid)-Conjugated 6-Aminofluorescein and Rhodamine Micelle as Macromolecular Fluorescent Probes for Micro-Tumors Detection and Imaging

Gahininath Y Bharate; Haibo Qin; Jun Fang

doi:10.3390/jpm12101650

Poly(Styrene-Co-Maleic Acid)-Conjugated 6-Aminofluorescein and Rhodamine Micelle as Macromolecular Fluorescent Probes for Micro-Tumors Detection and Imaging

J Pers Med. 2022 Oct 4;12(10):1650. doi: 10.3390/jpm12101650.

Authors

Gahininath Y Bharate^{1

2

3}, Haibo Qin³, Jun Fang³

Affiliations

¹ Admatius Innovations Pvt. Ltd., G.O. Squre, S.NO. 249/250, Office No. 207, Wakad, Pune 411057, India.
² SKE Labs, Survery No. 7/1, Jai Malhar Nagar, Thergaon, Pune 411033, India.
³ Laboratory of Microbiology and Oncology, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto 860-0082, Japan.

Abstract

Styrene-co-maleic acid (SMA) copolymer was evaluated as a polymer platform to conjugate with two fluorescent dyes, i.e., 6-aminofluorescein (AF) and Rhodamine (Rho); which spontaneously self-assembles in an aqueous medium and forms a micelle through a non-covalent interaction. These SMA-dye conjugates showed the nanosized micelle formation through dynamic light scattering (DLS) with discrete distributions having mean particle sizes of 135.3 nm, and 190.9 nm for SMA-AF, and SMA-Rho, respectively. The apparent molecular weight of the micelle was evaluated using Sephadex G-100 gel chromatography and it was found that the 49.3 kDa, and 28.7 kDa for SMA-AF, and SMA-Rho, respectively. Moreover, the biodistribution study showed the selective accumulation of the SMA-dye conjugates in the tumor of mice. Taken together, the SMA-dye conjugated micelles appear in high concentrations in the tumor by utilizing the enhanced permeability and retention (EPR) effect of the tumor-targeted delivery. These results indicate that SMA-dye conjugates have the advanced potential as macromolecular fluorescent probes for microtumor imaging by means of a photodynamic diagnosis.

Keywords: EPR effect; fluorescent probes; photodynamic diagnosis; polymer-dye conjugates; tumor imaging.

Grants and funding

This work was supported by Grants-in-Aid from the Ministry of Health, Welfare and Labour (No. 23000001, H 23-3) 3rd Cancer Study Project, and Japan Society for the Promotion of Science (JSPS) KAKENHI grant number 20015045, 20590049, and S0801085.