Glucosylated Polymeric Micelles Actively Target a Breast Cancer Model

Abstract

This work investigates the potential of glycosylation to actively target nanodrug delivery systems to adult solid tumors overexpressing glucose transporters. The highly hydrophobic fluorescent compound curcumin (CUR) is nanoencapsulated within polymeric micelles of pristine and glucosylated poly(ethylene oxide)‐poly(propylene oxide) block copolymers, and their interaction with breast cancer (BC) cells is investigated in vitro and in vivo. The aqueous solubility of CUR is increased more than 50 000‐fold and spherical nanoparticles display size in the 40 to 500 nm range, as determined by transmission electron microscopy and by dynamic light scattering, respectively. Uptake studies conducted in the BC cell line 4T1 in vitro demonstrate that glucosylation enhances nanoparticle internalization. Finally, the ability of unmodified and glucosylated polymeric micelles to accumulate in female BALB/c mice bearing 4T1‐induced tumors is compared by ex vivo bioimaging with auspicious results.

Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer

“…Instead, F127-Glu/FNZ PMs displayed an increase in size (~700 nm) with a unique monomodal population, after encapsulation of FNZ ( Table 1 ). On the other hand, PDI is a parameter that indicates the degree of polydispersity in the sample [ 32 , 33 , 34 , 35 ]. All PDI values obtained, corresponded to values less than 0.5, between 0.180 and 0.335 ( Table 1 ), indicating that PMs/FNZ were all suitable for monomodal distribution.…”

“…Z-pot is a relevant parameter of the degree of stability of the samples [ 32 , 33 , 34 , 35 ]. The Z-pot values for F127-Glu, T1307-Glu and T1307:F127 varied between −1.6 to −13.9 mV ( Table 1 ), which it is compatible with biological membranes for subsequent endocytosis.…”

“…The preparation of pristine and glucosylated (Glu) poly(ethyleneoxide)- b -poly(propyleneoxide) (PEO-PPO) PMs in aqueous or lipid dispersions (LPS), loaded or unloaded with FNZ, was carried out as we previously reported [ 32 , 33 , 34 , 35 ]. Briefly, 750 mg of pristine F127, F127-Glu [ 34 , 35 ], T1307-Glu [ 35 ], or T1307:F127 (50:50) were hydrated with 2.5 mL of H 2 O at room temperature. The preparation was left overnight at 4 °C and then the volume was completed, at room temperature, to 5.0 mL (final copolymer concentration of 15% w / v ).…”

“…Herein in the present work, we studied the capability of self-assembled amphiphilic PMs and mixed PMs based of pristine block copolymers of polyethyleneoxide-polypropyleneoxide (PEO-PPO) and their glycosylated derivatives [ 33 , 34 , 35 , 36 , 37 ], to improve the hydrosolubility and bioavailability of FNZ as possible candidate agent for the treatment of breast cancer. The glycosylation of PMs was previously for us, to promote the potential micelles-accumulation within the tumor as the result of a greater cellular uptake at the expense of the exacerbated increase in glucose metabolism in tumor cells and overexpression of GLUTs receptor [ 34 , 35 , 36 , 37 , 38 , 39 ].…”

T908 Polymeric Micelles Improved the Uptake of Sgc8-c Aptamer Probe in Tumor-Bearing Mice: A Co-Association Study between the Probe and Preformed Nanostructures

“…Poloxamers and poloxamines are the most investigated variant of nonionic polymers for the development of drug delivery and vaccine adjuvants. They are formed by a linear triblock of poly(ethylene oxide)-poly(propylene oxide) (PEO-PPO) and are found as unimers in the aqueous medium below the Critical Micelle Concentration (CMC) [31][32][33][34][35]. Above the CMC, copolymer aggregate to form nanomicelles consisting of a hydrophobic core of PPO chains, while the PEO chains form the hydrophilic shell [31][32][33][34][35].…”