Comparing cellular uptake and cytotoxicity of targeted drug carriers in cancer cell lines with different drug resistance mechanisms

Lei, Tingjun; Srinivasan, Supriya; Tang, Yuan; Manchanda, Romila; Nagesetti, Abhignyan; Fernandez-Fernandez, Alicia; McGoron, Anthony J.

doi:10.1016/j.nano.2010.11.004

Cited by 82 publications

(78 citation statements)

References 46 publications

(54 reference statements)

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“…11,12 Nanoparticles can reach and accumulate within the tumor site passively, exploiting leaky and imperfect tumor neovascularization and defective lymphatic drainage, 13,14 or actively, by functionalizing the surface of the nanoparticles with ligands specifically directed to targets expressed on tumor cells. [15][16][17][18] Before a nanomaterial can be deemed a suitable theranostic tool, it is necessary to assess its ability to enter the cell, to reach the desired intracellular compartment (wherein the drug will be liberated), and to remain in the cell for a time period sufficient to allow adequate diagnostic and therapeutic functions. In this respect, it is convenient to select the nanoparticle first for its potential as an "in cell" imaging agent and thereafter proceed with its "upgrade' to theranostics by adding a therapeutic function.…”

Section: Introductionmentioning

confidence: 99%

Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: effects of size and surface charge groups

Ekkapongpisit¹,

Giovia²,

Follo³

et al. 2012

IJN

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Background and methods Nanoparticles engineered to carry both a chemotherapeutic drug and a sensitive imaging probe are valid tools for early detection of cancer cells and to monitor the cytotoxic effects of anticancer treatment simultaneously. Here we report on the effect of size (10–30 nm versus 50 nm), type of material (mesoporous silica versus polystyrene), and surface charge functionalization (none, amine groups, or carboxyl groups) on biocompatibility, uptake, compartmentalization, and intracellular retention of fluorescently labeled nanoparticles in cultured human ovarian cancer cells. We also investigated the involvement of caveolae in the mechanism of uptake of nanoparticles. Results We found that mesoporous silica nanoparticles entered via caveolae-mediated endocytosis and reached the lysosomes; however, while the 50 nm nanoparticles permanently resided within these organelles, the 10 nm nanoparticles soon relocated in the cytoplasm. Naked 10 nm mesoporous silica nanoparticles showed the highest and 50 nm carboxyl-modified mesoporous silica nanoparticles the lowest uptake rates, respectively. Polystyrene nanoparticle uptake also occurred via a caveolae-independent pathway, and was negatively affected by serum. The 30 nm carboxyl-modified polystyrene nanoparticles did not localize in lysosomes and were not toxic, while the 50 nm amine-modified polystyrene nanoparticles accumulated within lysosomes and eventually caused cell death. Ovarian cancer cells expressing caveolin-1 were more likely to endocytose these nanoparticles. Conclusion These data highlight the importance of considering both the physicochemical characteristics (ie, material, size and surface charge on chemical groups) of nanoparticles and the biochemical composition of the cell membrane when choosing the most suitable nanotheranostics for targeting cancer cells.

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Section: Introductionmentioning

confidence: 99%

Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: effects of size and surface charge groups

Ekkapongpisit¹,

Giovia²,

Follo³

et al. 2012

IJN

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“…Polymeric NPs with targeting ligands are promising candidates for cancer therapy because they can preferentially localize in tumor tissue rather than in non-cancerous tissues in the body (Pardridge, 2007;Pulkkinen et al, 2008). One strategy that has been explored is the application of antibodytargeted NPs (Kocbek et al, 2007;Chen et al, 2008;Sun et al, 2008;Fay et al, 2011;Lei et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Preparation of camptothecin-loaded targeting nanoparticles and their antitumor effects on hepatocellular carcinoma cell line H22

Yang

Yan

et al. 2014

Drug Delivery

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Camptothecin (CPT) is an effective anticancer agent against various cancers but the clinical application is limited because of its poor water solubility, low bioavailability and severe toxic side effects. The aim of the present study was to evaluate the feasibility of using targeted NPs as a high-performance CPT delivery system that targets liver cancer cells through intravenous (i.v.) administration route. CPT was incorporated into biotin-F127-PLA or F127-PLA polymeric nanoparticles (NPs) by a dialysis method. The preparation of the targeting NPs was performed by conjugating biotin-F127-PLA NPs with anti-3A5 antibody. The antitumor effect of the CPTloaded nanoparticles against H22 cells in vitro was determined using an MTT assay. Tissue distribution and tumor inhibition in vivo were also evaluated. Survivin mRNA expression was assessed by real-time polymerase chain reaction. Results showed that the targeted CPT NPs exhibited regular spherical shapes with a mean diameter of approximately 180 nm. In vitro release of the targeted CPT NPs exhibited an initial burst (40%) within 12 h, followed by a slow release. Cytotoxicity test against H22 cells indicated that the targeted CPT NPs exerted significant antitumor effects. Compared with free CPT and non-targeted CPT NPs, the targeted CPT NPs showed superior inhibition ratio against tumor in vivo, which may be associated with reduced survivin mRNA expression. The results suggested that the new targeted CPT NPs may be a promising injectable delivery system for cancer therapy.

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“…This method of localizing drugs to the tumor tissue is a type of passive targeting. 9 However, trapping drugs into carriers also prevents them from being recognized by cellular efflux pumps, such as P-glycoprotein (P-gp), and hence helps overcome MDR in resistant tumors. 10 With proper design, the therapeutic potential of drug carriers can be further enhanced to achieve active targeting capability.…”

mentioning

confidence: 99%

“…By tagging them with appropriate ligands such as monoclonal antibodies (mAbs), such drug carriers can specifically interact with cancer cell membrane receptors, 11 thus allowing the drug to be released specifically inside the tumor by receptor-mediated endocytosis. 9 Among all targeting moieties, mAbs are the most widely investigated for tumor targeting. 12 Initially, mAbs were conjugated directly to anticancer compounds, 13,14 although direct conjugation allows few antibodies to be linked to the drug 15 and usually adversely affect the drug's pharmacological potency.…”

mentioning

confidence: 99%

Targeted multidrug delivery system to overcome chemoresistance in breast cancer

Tang

Soroush

Tong

et al. 2017

IJN

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Chemotherapy has been widely used in breast cancer patients to reduce tumor size. However, most anticancer agents cannot differentiate between cancerous and normal cells, resulting in severe systemic toxicity. In addition, acquired drug resistance during the chemotherapy treatment further decreases treatment efficacy. With the proper treatment strategy, nanodrug carriers, such as liposomes/immunoliposomes, may be able to reduce undesired side effects of chemotherapy, to overcome the acquired multidrug resistance, and to further improve the treatment efficacy. In this study, a novel combinational targeted drug delivery system was developed by encapsulating antiangiogenesis drug bevacizumab into liposomes and encapsulating chemotherapy drug doxorubicin (DOX) into immunoliposomes where the human epidermal growth factor receptor 2 (HER2) antibody was used as a targeting ligand. This novel combinational system was tested in vitro using a HER2 positive and multidrug resistant breast cancer cell line (BT-474/MDR), and in vivo using a xenograft mouse tumor model. In vitro cell culture experiments show that immunoliposome delivery led to a high cell nucleus accumulation of DOX, whereas free DOX was observed mostly near the cell membrane and in cytoplasm due to the action of P-gp. Combining liposomal bevacizumab with immunoliposomal DOX achieved the best tumor growth inhibition and the lowest toxicity. Tumor size decreased steadily within a 60-day observation period indicating a potential synergistic effect between DOX and bevacizumab through the targeted delivery. Our findings clearly indicate that tumor growth was significantly delayed in the combinational liposomal drug delivery group. This novel combinational therapy has great potential for the treatment of patients with HER2/MDR double positive breast cancer.

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Comparing cellular uptake and cytotoxicity of targeted drug carriers in cancer cell lines with different drug resistance mechanisms

Cited by 82 publications

References 46 publications

Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: effects of size and surface charge groups

Biocompatibility, endocytosis, and intracellular trafficking of mesoporous silica and polystyrene nanoparticles in ovarian cancer cells: effects of size and surface charge groups

Preparation of camptothecin-loaded targeting nanoparticles and their antitumor effects on hepatocellular carcinoma cell line H22

Targeted multidrug delivery system to overcome chemoresistance in breast cancer

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