Sweetness Reduces Cytotoxicity and Enables Faster Cellular Uptake of Sub-30 nm Amphiphilic Nanoparticles

Author(s)

de Castro, Carlos E. ^[1] ; Ribeiro, Caroline A. S. ^[1] ; da Silva, Maria C. C. ^[1] ; Dal-Bo, Alexandre Goncalves ^[2] ; Giacomelli, Fernando C. ^[1]

Affiliation

^[1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210580 Santo Andre, SP - Brazil

^[2] Univ Extremo Sul Catarinense UNESC, Ave Univ 1105, BR-88806000 Criciuma, SC - Brazil

• Document type: Journal article
• Source: Langmuir; v. 35, n. 24, p. 8060-8067, JUN 18 2019.
• Web of Science Citations: 0

Abstract

Glycoconjugates are versatile entities used for the manufacturing of targeted drug delivery nanocontainers because of their outstanding capability to bind to lectins, which are proteins that can be found overexpressed in the membranes of unhealthy cells. The assisted attachment to pathological cells can further enable a more efficient intracellular delivery of loaded active agents, thereby reducing side effects that commonly compromise chemotherapies. In this framework, azide-terminated polyethylene oxide (PEO) chains coupled to a 22-carbon chain were synthesized (azide-PEO900-docosanoate). The resulting amphiphile was further functionalized by introducing different sugar moieties to the PEO chains via the click chemistry approach. Sub-30 nm, negatively charged, and spherical nanoparticles were prepared in water by self-assembly of the synthesized molecules using the straightforward nanoprecipitation protocol. The produced entities do not induce hemolysis in red blood cells at c <= 200 mu g mL(-1), and they are not cytotoxic to healthy cells {[}telomerase immortalized rhesus fibroblasts (Telo-RF)] at c <= 50 mu g mL(-1). The sugar-decorated nanoparticles are less cytotoxic compared with their naked counterparts at the concentration range assessed. The kinetics of cellular uptake of both entities into normal (Telo-RF) and tumor (HeLa) cells were monitored via fluorescence microscopy and flow cytometry. The nanoparticles are internalized faster in cancer cells than in normal cells, regardless of functionalization. Moreover, the functionalized nanoparticles are internalized faster in HeLa cells, while the reverse was observed in healthy Telo-RF cells. The distinct surface characteristics of the assemblies create an opportunity to expedite the uptake of nanoparticles particularly by tumor cells, and this accordingly can lead to a more effective intracellular delivery of therapeutic molecules loaded into nanoparticle's reservoirs. (AU)

• FAPESP's process: 15/24686-4 - THE INFLUENCE OF SURFACE CHEMISTRY AND PROTEIN CORONA IN THE CELLULAR UPTAKE OF NON-TARGETED POLYMERIC NANOPARTICLES
• Grantee: Carlos Eduardo de Castro
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/00459-4 - Biophysicochemical interactions at the nanobiointerface: the effect of surface features and protein corona on the cellular uptake of polymeric assemblies
• Grantee: Fernando Carlos Giacomelli
• Support Opportunities: Regular Research Grants