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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

ear-Infrared Fluorescent Micelles from Poly(norbornene) Brush Triblock Copolymers for Nanotheranostic

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Braga, Carolyne B. [1, 2, 3] ; Pilli, Ronaldo A. [1] ; Ornelas, Catia [1] ; Weck, Marcus [2, 3]
Total Authors: 4
[1] Univ Estadual Campinas, Inst Chem, UNICAMP, BR-13083970 Campinas, SP - Brazil
[2] NYU, Dept Chem, New York, NY 10003 - USA
[3] NYU, Mol Design Inst, New York, NY 10003 - USA
Total Affiliations: 3
Document type: Journal article
Source: Biomacromolecules; v. 22, n. 12, p. 5290-5306, DEC 13 2021.
Web of Science Citations: 0

This contribution describes the design and synthesis of multifunctional micelles based on amphiphilic brush block copolymers (BBCPs) for imaging and selective drug delivery of natural anticancer compounds. Well-defined BBCPs were synthesized via one-pot multi-step sequential grafting-through ring-opening metathesis polymerization (ROMP) of norbornene-based macroinitiators. The norbornenes employed contain a poly(ethylene glycol) methyl ether chain, an alkyl bromide chain, and/or a near-infrared (NIR) fluorescent cyanine dye. After block copolymerization, post-polymerization transformations using bromide-azide substitution, followed by the strain-promoted azide-alkyne cycloaddition (SPAAC) allowed for the functionalization of the BBCPs with the piplartine (PPT) moiety, a natural product with well-documented cytotoxicity against cancer cell lines, via an ester linker between the drug and the polymer side chain. The amphiphilic BBCPs self-assembled in aqueous media into nano-sized spherical micelles with neutral surface charges, as confirmed by dynamic light scattering analysis and transmission electron microscopy. During self-assembly, paclitaxel (PTX) could be effectively encapsulated into the hydrophobic core to form stable PTX-loaded micelles with high loading capacities and encapsulation efficiencies. The NIR fluorescent dye-containing micelles exhibited remarkable photophysical properties, excellent colloidal stability under physiological conditions, and a pH-induced disassembly under slightly acidic conditions, allowing for the release of the drug in a controlled manner. The in vitro studies demonstrated that the micelles without the drug (blank micelles) are biocompatible at concentrations of up to 1 mg mL(-1) and present a high cellular internalization capacity toward MCF-7 cancer cells. The drug-functionalized micelles showed in vitro cytotoxicity comparable to free PPT and PTX against MCF-7 and PC3 cancer cells, confirming efficient drug release into the tumor environment upon cellular internalization. Furthermore, the drug-functionalized micelles exhibited higher selectivity than the pristine drugs and preferential cellular uptake in human cancer cell lines (MCF-7 and PC3) when compared to the normal breast cell line (MCF10A). This study provides an efficient strategy for the development of versatile polymeric nanosystems for drug delivery and image-guided diagnostics. Notably, the easy functionalization of BBCP side chains via SPAAC opens up the possibility for the preparation of a library of multifunctional systems containing other drugs or functionalities, such as target groups for recognition. (AU)

FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
Grantee:Licio Augusto Velloso
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 19/13104-5 - Planning and synthesis of inhibitors based on biological targets: the case of neglected kinases
Grantee:Ronaldo Aloise Pilli
Support Opportunities: Regular Research Grants
FAPESP's process: 14/50906-9 - INCT 2014: in Functional Complex Materials
Grantee:Fernando Galembeck
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 18/24020-4 - Polynorbornene-goniothalamin and polynorbornene-piplartine conjugates for cancer therapy
Grantee:Carolyne Brustolin Braga
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 17/06146-8 - Development of nanocarriers based on dendrimers and polymer nanoparticles for selective delivery of goniothalamin, piplartine and Monastrol
Grantee:Carolyne Brustolin Braga
Support Opportunities: Scholarships in Brazil - Post-Doctoral