Intracellular Targeting of Poly Lactic-Co-Glycolic Acid Nanoparticles by Surface Functionalization with Peptides

2021 ◽  
Vol 17 (7) ◽  
pp. 1320-1329
Author(s):  
Thaís Dolzany de Oliveira ◽  
Luiz R. Travassos ◽  
Denise Costa Arruda ◽  
Dayane Batista Tada

Nanoparticles (NPs) are a promising strategy for delivering drugs to specific sites because of their tunable size and surface chemistry variety. Among the availablematerials, NPs prepared with biopolymers are of particular interest because of their biocompatibility and controlled release of encapsulated drugs. Poly lactic-co-glycolic acid (PLGA) is one of the most widely used biopolymers in biomedical applications. In addition to material choice modulation of the interaction between NPs and biological systems is essential for the safety and effective use of NPs. Therefore, this work focused on evaluating different surface functionalization strategies to promote cancer cell uptake and intracellular targeting of PLGA NPs. Herein, cell-penetrating peptides (CPPs) were shown to successfully drive PLGA NPs to the mitochondria and nuclei. Furthermore, the functionalization of PLGA NPs with peptide AC-1001 H3 (GQYGNLWFAY) was proven to be useful for targeting actin filaments. The PLGA NPs cell internalization mechanism by B16F10-Nex2 cells was identified as caveolae-mediated endocytosis, which could be inhibited by the presence of methyl-β-cyclodextrin. Notably, when peptide C (CVNHPAFAC) was used to functionalize PLGA NPs, none of the tested inhibitors could avoid cell internalization of PLGA NPs. Therefore, we suggest this peptide as a promising surface modification agent for enhancing drug delivery to cancer cells. Finally, PLGA NPs showed slow release kinetics and low cytotoxic profile, which, combined with the surface functionalization strategies addressed in this study, highlight the potential of PLGA NPs as a drug delivery platform for improving cancer therapy.

2015 ◽  
Vol 3 (37) ◽  
pp. 7449-7456 ◽  
Author(s):  
Xiang Li ◽  
Qiuhong Zhang ◽  
Zeeshan Ahmad ◽  
Jie Huang ◽  
Zhaohui Ren ◽  
...  

Nd3+ doped CaTiO3 nanostructures serve as a promising drug delivery platform with the potential to monitor drug release kinetics by detecting the tissue-penetrating NIR emission.


2016 ◽  
Vol 696 ◽  
pp. 245-249
Author(s):  
Ahmed El-Ghannam

Silica-calcium-phosphate composite (SCPC) is a drug delivery platform that has successfully demonstrated the ability to bind and release several therapeutics including antibiotics, peptides, anticancer drugs, and growth factors. It has successfully demonstrated a unique capacity for bone regeneration. The present studies address the effect of the phosphate and silicate functional groups on drug binding and controlled release kinetics of Cisplatin (Cis). Moreover, the roles of ceramic composition and resorbability on rhBMP2 release kinetics and bone regeneration in a critical size calvarial defect in rabbit is presented.


2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Nopparuj Soomherun ◽  
Narumol Kreua-ongarjnukool ◽  
Sorayouth Chumnanvej ◽  
Saowapa Thumsing

Poly(D,L-lactic-co-glycolic acid) (PLGA) is an important material used in drug delivery when controlled release is required. The purpose of this research is to design and characterize PLGA microparticles (PLGA MPs) implants for the controlled release of nicardipine hydrochloride (NCH) in vitro. This study used the water-in-oil-in-water (w1/o/w2) double emulsion and solvent diffusion/evaporation approach to prepare PLGA MPs. Optimal processing conditions were found, such as polymer content, surfactant type, stabilizer concentration, inner and outer aqueous phase volumes, and stirring speed. The PLGA MPs for use as nicardipine hydrochloride (NCH) loading and release had spherical morphology, and the average diameter was smaller than 5.20±0.25 μm. The release kinetics were modeled to elucidate the possible mechanism of drug release. In vitro release studies indicated that the NCH release rate is slow and continuous. PLGA MPs are an interesting alternative drug delivery system, especially for use with NCH for biomedical applications.


NANO ◽  
2014 ◽  
Vol 09 (01) ◽  
pp. 1450009 ◽  
Author(s):  
CHRISTIN M. GRABINSKI ◽  
JATUPORN SALAKLANG ◽  
CAROL M. GARRETT ◽  
AMANDA M. SCHRAND ◽  
ALKE PETRI-FINK ◽  
...  

Superparamagnetic iron oxide nanoparticles (SPIONs) are used in many biological applications, which necessitate intracellular targeting. Here, we investigate intracellular localization and gene expression in HeLa cells after treatment with functionalized SPIONs. Functional groups investigated included positive amino propyl silane (APS), polyethylene glycol and targeting peptides: nuclear targeting peptide (NTP) and/or cancer cell uptake promoting peptide (cRGD). Results revealed that the intracellular localization of SPIONs was strongly dependent on the surface chemistry. Nuclear targeted SPIONs functionalized with only NTP or both NTP and cRGD were mostly localized in perinuclear endosomes with a small fraction entering the nucleus. The biocompatibility of cells after treatment was also dependent on surface chemistry, where SPIONs functionalized with both NTP and cRGD exhibited a more significant reduction of cell proliferation compared to NTP or cRGD individually. Interestingly, gene expression after treatment with SPIONs was similar, regardless of the surface functionalization or intracellular localization. The results of this study showed that cellular uptake and intracellular localization predominantly depended on the surface chemistry, while gene expression exhibited a more generic response to SPION treatment.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Meta A. Simon ◽  
Erlina Anggraeni ◽  
Felycia Edi Soetaredjo ◽  
Shella Permasari Santoso ◽  
Wenny Irawaty ◽  
...  

AbstractSustainable development of drug delivery materials with good biocompatibility and controlled-release is a popular topic among researchers. In this research study, we demonstrated the potential of the metal-organic framework, that is MIL-100(Fe), as a drug delivery platform for isoniazid (INH). The MIL-100(Fe) was prepared by using the hydrofluoric acid-free hydrothermal method. Several physical measurements were conducted to characterize the MIL-100(Fe), including x-ray diffraction (XRD), scanning electron microscopy (SEM), nitrogen sorption, and thermal-gravimetric (TG). The synthesized MIL-100(Fe) has octahedron-shaped particles with superior properties, that is large surface area (1456.10 m2/g) and pore volume (1.25 cm3/g). The drug loading rate and capacity were determined by means of adsorption kinetic and isotherm. The studied INH@MIL-100(Fe) adsorption system kinetics follow the pseudo-first-order model, while the isotherm system follows the Langmuir model with the maximum adsorption capacity of 128.5 mg/g at 30 °C. MIL-100(Fe) shows adequate biocompatibility, also exhibits a reasonable and controlled drug release kinetics. The results obtained show that MIL-100 (Fe) can be a good choice of drug delivery platform among other available platforms.


2019 ◽  
Vol 20 (1) ◽  
pp. 204 ◽  
Author(s):  
Giuseppe Cappellano ◽  
Cristoforo Comi ◽  
Annalisa Chiocchetti ◽  
Umberto Dianzani

Tolerogenic vaccines are aimed at inhibiting antigen-specific immune responses. Antigen-loaded nanoparticles (NPs) have been recently emerged as ideal tools for tolerogenic vaccination because their composition, size, and capability of loading immunomodulatory molecules can be readily exploited to induce peripheral tolerance. Among polymeric NPs, poly(lactic-co-glycolic acid) (PLGA) NPs have the advantage of currently holding approval for several applications in drug delivery, diagnostics, and other clinical uses by the Food and Drug Administration (FDA). PLGA-NPs are non-toxic and display excellent biocompatibility and biodegradability properties. Moreover, surface functionalization may improve their interaction with biological materials, thereby optimizing targeting and performance. PLGA-NPs are the most extensively studied in pre-clinical model in the field of tolerogenic vaccination. Thus, this review describes their potential applications in the treatment of autoimmune diseases.


Sign in / Sign up

Export Citation Format

Share Document