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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: Langmuir; v. 35, n. 24, p. 8060-8067, JUN 18 2019.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 15/24686-4 - Investigação de efeitos de superfície e presença de coroa protéica no processo de internalização celular de sistemas poliméricos nanoestruturados
• Beneficiário: Carlos Eduardo de Castro
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/00459-4 - Interações biofisicoquímicas na nanobiointerface: a influência das características superficiais e da presença de coroa protéica no processo de internalização celular de nanomateriais
• Beneficiário: Fernando Carlos Giacomelli
• Modalidade de apoio: Auxílio à Pesquisa - Regular