Cytotoxicity and Cellular Internalization of Epirubicin-Loaded Folate-Conjugated Pullulan Acetate Nanoparticles in Cancer Cells

2016 ◽  
Vol 8 (11) ◽  
pp. 2029-2036 ◽  
Author(s):  
Hongli Chen ◽  
Yajing Jia ◽  
Wenbin Nan ◽  
Hongbo Tang ◽  
Zhimin Zhou ◽  
...  
2011 ◽  
Vol 22 (9) ◽  
pp. 095101 ◽  
Author(s):  
Radu Marches ◽  
Carole Mikoryak ◽  
Ru-Hung Wang ◽  
Paul Pantano ◽  
Rockford K Draper ◽  
...  

2014 ◽  
Vol 2 (1) ◽  
pp. 36-51 ◽  
Author(s):  
Radhika Raveendran ◽  
C. K. S. Pillai ◽  
G. S. Bhuvaneshwar ◽  
Chandra P. Sharma

Author(s):  
Elham Kamalkazemi ◽  
Fereydoon Abedi - Gaballu ◽  
Tala Farid Mohammad Hosseini ◽  
Ali Mohammadi ◽  
Behzad Mansoori ◽  
...  

: Lipid-based nanoparticles as drug delivery carriers have been mainly used for delivery of anti-cancer therapeutic agents. Lipid-based nanoparticles, due to their smaller particle size and similarity to cell membranes, are readily internalized into cancer cells. Interestingly, cancer cells also overexpress receptors for specific ligands including folic acid, hyaluronic acid, and transferrin on their surface. This allows the use of these ligands for surface modification of the lipid-based nanoparticle. These modifications then allow the specific recognition of these ligand-coated nanoparticles by their receptors on cancer cells allowing the targeted gradual intracellular accumulation of the functionalized nanoplatforms. These interactions could eventually enhance the internalization of desired drugs via increasing ligand-receptor mediated cellular uptake of the nanoplatforms. The cellular internalization of the nanoplatforms also varies and depends on their physicochemical properties including particle size, zeta potential, and shape. The cellular uptake is also influenced by the types of ligand internalization pathway utilized by cells such as phagocytosis, macropinocytosis, and multiple endocytosis pathways. In this review, we will classify and discuss lipid based nanoparticles engineered to express specific ligands, and are recognized by their receptors on cancer cell, and their cellular internalization pathways. Moreover, the intracellular fate of nanoparticles decorated with specific ligands and the best internalization pathways (caveolae mediated endocytosis) for safe cargo delivery will be discussed.


Metallodrugs ◽  
2016 ◽  
Vol 1 (1) ◽  
Author(s):  
Andrea Pettenuzzo ◽  
Rebecca Pigot ◽  
Luca Ronconi

AbstractGlucose is a key source of energy and an essential nutrient for cell growth. Rapidly dividing cancer cells are well-known to require more nutrients and energy than normal ones to sustain their higher proliferation rates, and glucose is no exception. Therefore, the biomolecules involved in the promotion/regulation of the glycolytic flux may be regarded as potential targets for tackling tumor progression. Among all, glucose transporters (GLUTs), devoted to the recognition and cellular internalization of glucose, are largely overexpressed in tumors, thus indicating glycolysis as the major anaerobic glucose metabolism. Accordingly, such increased demand of glucose by fast-proliferating cancer cells makes it very attractive to selectively target tumor sites. In particular, tailored glucose-like substrates can be conjugated to chemotherapeutics (including metal-containing anticancer agents) so as to attain the site-specific delivery of drugs into the affected tissues. Progress in the development of metal-based glycoconjugates are here summarized and discussed.


2020 ◽  
Vol 21 (18) ◽  
pp. 6721
Author(s):  
Sheikh Tanzina Haque ◽  
Rowshan Ara Islam ◽  
Siew Hua Gan ◽  
Ezharul Hoque Chowdhury

Background: The limitations of conventional treatment modalities in cancer, especially in breast cancer, facilitated the necessity for developing a safer drug delivery system (DDS). Inorganic nano-carriers based on calcium phosphates such as hydroxyapatite (HA) and carbonate apatite (CA) have gained attention due to their biocompatibility, reduced toxicity, and improved therapeutic efficacy. Methods: In this study, the potential of goose bone ash (GBA), a natural derivative of HA or CA, was exploited as a pH-responsive carrier to successfully deliver doxorubicin (DOX), an anthracycline drug into breast cancer cells (e.g., MCF-7 and MDA-MB-231 cells). GBA in either pristine form or in suspension was characterized in terms of size, morphology, functional groups, cellular internalization, cytotoxicity, pH-responsive drug (DOX) release, and protein corona analysis. Results: The pH-responsive drug release study demonstrated the prompt release of DOX from GBA through its disintegration in acidic pH (5.5–6.5), which mimics the pH of the endosomal and lysosomal compartments as well as the stability of GBA in physiological pH (pH 7.5). The result of DOX binding with GBA indicated an increment in binding affinity with increasing concentrations of DOX. Cell viability and cytotoxicity analysis showed no innate toxicity of GBA particles. Both qualitative and quantitative cellular uptake analysis in both cell lines displayed an enhanced cellular internalization of DOX-loaded GBA compared to free DOX molecules. The protein corona spontaneously formed on the surface of GBA particles exhibited its affinity toward transport proteins, structural proteins, and a few other selective proteins. The adsorption of transport proteins could extend the circulation half-life in biological environment and increase the accumulation of the drug-loaded NPs through the enhanced permeability and retention (EPR) effect at the tumor site. Conclusion: These findings highlight the potential of GBA as a DDS to successfully deliver therapeutics into breast cancer cells.


2019 ◽  
Vol 7 (1) ◽  
pp. 336-346
Author(s):  
Dong Chen ◽  
Huangyong Jiang ◽  
Dongbo Guo ◽  
Wumaier Yasen ◽  
Junping Ao ◽  
...  

We fabricated a novel nanomedicine possessing both anti-biofouling feature and relatively high cellular internalization.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Yan Baglo ◽  
Lars Hagen ◽  
Anders Høgset ◽  
Finn Drabløs ◽  
Marit Otterlei ◽  
...  

Bleomycin is a cytotoxic chemotherapeutic agent widely used in cancer treatment. However, its efficacy in different cancers is low, possibly due to limited cellular internalization. In this study, a novel approach known as photochemical internalization (PCI) was explored to enhance bleomycin delivery in bladder cancer cells (human T24 and rat AY-27), as bladder cancer is a potential indication for use of PCI with bleomycin. The PCI technique was mediated by the amphiphilic photosensitizer disulfonated tetraphenyl chlorin (TPCS2a) and blue light (435 nm). Two additional strategies were explored to further enhance the cytotoxicity of bleomycin; a novel peptide drug ATX-101 which is known to impair DNA damage responses, and the protease inhibitor E-64 which may reduce bleomycin degradation by inhibition of bleomycin hydrolase. Our results demonstrate that the PCI technique enhances the bleomycin effect under appropriate conditions, and importantly we show that PCI-bleomycin treatment leads to increased levels of DNA damage supporting that the observed effect is due to increased bleomycin uptake. Impairing the DNA damage responses by ATX-101 further enhances the efficacy of the PCI-bleomycin treatment, while inhibiting the bleomycin hydrolase does not.


2013 ◽  
Vol 8 (1) ◽  
pp. 208 ◽  
Author(s):  
Stuart J Corr ◽  
Mustafa Raoof ◽  
Brandon T Cisneros ◽  
Oleksandr Kuznetsov ◽  
Katheryn Massey ◽  
...  

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Li-Juan Ma ◽  
Ruichao Niu ◽  
Xi Wu ◽  
Jun Wu ◽  
En Zhou ◽  
...  

AbstractClinical translation of poly (lactic-co-glycolic acid) (PLGA)-based nanomedicine is limited, partly because of the poor delivery efficiency resulting from non-specific phagocytosis by phagocytes. Understanding the nanoparticle interplay between cancer cells and immune cells remains largely elusive. In this study, a quantitative investigation on cellular internalization of fluorescent PLGA particles (100 nm, 500 nm, and 1 µm) against laryngeal carcinoma cells with or without monocytes/macrophages in monoculture or co-culture systems was first performed. PLGA particles at concentrations of 5–20 µg/mL show superior biocompatibility except for 500 nm and 1 µm PLGA particles at 20 µg/mL slightly reduce cell viability. Microscopic observation has discovered all three sizes of particles are effectively ingested by both cancer cells and macrophages; however, quantitative fluorescence examination has disclosed that the uptake index of cancer cells (mean intracellular particle fluorescence per cancer cell normalized to that of per macrophage) is substantially declined for all PLGA particles in co-cultures compared to that in monocultures (1.35–1.05, 1.50–0.59, and 1.4–0.47 for 100 nm, 500 nm, and 1 µm particles, respectively). Quantitative analysis using flow cytometry further confirmed the reduced uptake index of cancer cells in co-cultures, but higher particle counts per macrophage. It has also been found that the formation of multinucleated giant cells via the fusion of macrophages increased after PLGA treatment, which could be further exploited as a potential approach for tumor drug delivery. Overall, these findings provide new insights into the interaction of nanoparticle-immune-cancer cells, which may facilitate the application of PLGA-based nanocarriers for the treatment of laryngeal carcinoma.


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