Nanocarriers for Cytosolic Drug and Gene Delivery in Cancer Therapy

Palakurthi, Srinath; Yellepeddi, Venkata K.; Kumar, Ajay

doi:10.5772/12918

Cited by 4 publications

(3 citation statements)

References 112 publications

(109 reference statements)

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“…11 Uptake of nanoparticles beyond this size can be triggered with the aid of a nuclear localization signal (NLS). 12 Gold nanoparticles functionalized with an arginine-glycine-aspartic (RGD) peptide and NLS peptide have been used for cancer cell nuclear targeting. 13 Most of the past studies focus on receptor targeting while few on nuclear targeting because of the challenges in the nuclear delivery of nanoparticles.…”

mentioning

confidence: 99%

Nuclear Targeting Dynamics of Gold Nanoclusters for Enhanced Therapy of HER2⁺ Breast Cancer

2011

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Recent advances in fluorescent metal nanoclusters have spurred tremendous interest in nanomedicine due to the ease of fabrication, excellent biocompatibility, and, more importantly, excellent wavelength-dependent tunability. Herein, we report our findings on fluorescent BSA-protected gold nanoclusters (AuNCs), ∼2 nm in size conjugated with Herceptin (AuNCs-Her), for specific targeting and nuclear localization in ErbB2 over-expressing breast cancer cells and tumor tissue as a novel fluorescent agent for simultaneous imaging and cancer therapy. More interestingly, we found that AuNCs-Her could escape the endolysosomal pathway and enter the nucleus of cancer cells to enhance the therapeutic efficacy of Herceptin. We elucidate the diffusion characteristics (diffusion time and number of diffusers) and concentration of the fluorescing clusters in the nucleus of live cells. Our findings also suggest that the nuclear localization effect of AuNCs-Her enhances the anticancer therapeutic efficacy of Herceptin as evidenced by the induction of DNA damage. This study not only discusses a new nanomaterial platform for nuclear delivery of drugs but also provides important insights on nuclear targeting for enhanced therapy.

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confidence: 99%

Nuclear Targeting Dynamics of Gold Nanoclusters for Enhanced Therapy of HER2⁺ Breast Cancer

2011

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“…In an animal study by our group, toxicity of PLA based MTX microneedle implants were evaluated in rabbit eyes [8]. The micro-implants were well tolerated without any sign of inflammation but degraded rapidly in the in vivo conditions.…”

Section: Existing Intravitreal Devicesmentioning

confidence: 99%

Development of Chitosan and Polylactic Acid Based Methotrexate Intravitreal Micro-Implants to Treat Primary Intraocular Lymphoma: An In Vitro Study

Manna

Augsburger

Corrêa

et al. 2014

Journal of Biomechanical Engineering

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Primary intraocular lymphoma (PIOL) is an uncommon but clinically and pathologically distinct form of non-Hodgkin's lymphoma. It provides a therapeutic challenge because of its diverse clinical presentations and variable clinical course. Currently available treatments for PIOL include intravenous multiple drug chemotherapy, external beam radiation therapy, and intravitreal methotrexate (MTX) injection. Each intravitreal injection of MTX is associated with potentially toxic peaks and subtherapeutic troughs of intraocular MTX concentration. Repetitive injections are required to maintain therapeutic levels of MTX in the eye. A sustained release drug delivery system is desired for optimized therapeutic release (0.2-2.0 μg/day) of MTX for over a period of 1 month to achieve effective treatment of PIOL. This study reports development of a unique intravitreal micro-implant, which administers therapeutic release of MTX over a period of 1 month. Chitosan (CS) and polylactic acid (PLA) based micro-implants are fabricated for different MTX loadings (10%, 25%, and 40% w/w). First, CS and MTX mixtures are prepared for different drug loadings, and lyophilized in Tygon® tubing to obtain CS-MTX fibers. The fibers are then cut into desired micro-implant lengths and dip coated in PLA for a hydrophobic surface coating. The micro-implant is characterized using optical microscopy, scanning electron microscopy (SEM), time of flight-secondary ion mass spectroscopy (ToF-SIMS), and differential scanning calorimetry (DSC) techniques. The release rate studies are carried out using a UV-visible spectrophotometer. The total release durations for 10%, 25%, and 40% w/w uncoated CS-MTX micro-implants are only 19, 29, and 32 h, respectively. However, the therapeutic release durations for 10%, 25%, and 40% w/w PLA coated CS-MTX micro-implants significantly improved to 58, 74, and 66 days, respectively. Thus, the PLA coated CS-MTX micro-implants are able to administer therapeutic release of MTX for more than 50 days. The release kinetics of MTX from the coated micro-implants is explained by (a) the Korsmeyer-Peppas and zero order model fit (R2 ∼ 0.9) of the first 60% of the drug release, which indicates the swelling of polymer and initial burst release of the drug; and (b) the first order and Higuchi model fit (R2 ∼ 0.9) from the tenth day to the end of drug release, implying MTX release in the therapeutic window depends on its concentration and follows diffusion kinetics. The PLA coated CS-MTX micro-implants are able to administer therapeutic release of MTX for a period of more than 1 month. The proposed methodology could be used for improved treatment of PIOL.

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“…There is an evidence that endocytosis (8) plays an important role, although not all of the entry mechanisms are well understood. The most common endocytosis used by nanocarriers is clathrin-mediated endocytosis through endocytic route receptor [23].…”

Section: Physiological Barriers For Sirnamentioning

confidence: 99%

Applications of Lipidic and Polymeric Nanoparticles for siRNA Delivery

Şenel¹,

Büyükköroğlu²

2019

Antisense Therapy

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The antisense technology that emerged with the discovery of RNA interference nearly 20 years ago has gained a significant place in gene therapy. siRNA, one of two important components of RNA interference, efficiently downregulates gene expression in human cells, so it has the potential to eradicate disease. siRNA delivery systems, which can be applied both systemically and locally in different diseases, have gained significant importance. Naked small RNAs can be delivered directly to cells, but because of their instability, exposure to enzyme degradation, and difficulties in reaching/entering the target cell or tissue in blood stream, these initiatives are failing. For this reason, the method of delivery or encapsulation of siRNA is usually required. Various nanoparticles, nanocapsules, emulsions, micelle systems, metal ion nanoparticles, and nanoconjugates have been used for siRNA delivery. In these transport systems, lipidic and polymeric systems are very attractive due to their advantages such as being biodegradable and biocompatible, safety, being able to electrostatically bind to RNA, long-term stability, well-illuminated structure and features, simple and easy production, etc. Issues such as particle size, zeta potential, and stability of siRNA-loaded system should be taken into consideration in the development of siRNA delivery systems.

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Nanocarriers for Cytosolic Drug and Gene Delivery in Cancer Therapy

Cited by 4 publications

References 112 publications

Nuclear Targeting Dynamics of Gold Nanoclusters for Enhanced Therapy of HER2⁺ Breast Cancer

Nuclear Targeting Dynamics of Gold Nanoclusters for Enhanced Therapy of HER2⁺ Breast Cancer

Development of Chitosan and Polylactic Acid Based Methotrexate Intravitreal Micro-Implants to Treat Primary Intraocular Lymphoma: An In Vitro Study

Applications of Lipidic and Polymeric Nanoparticles for siRNA Delivery

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Nanocarriers for Cytosolic Drug and Gene Delivery in Cancer Therapy

Cited by 4 publications

References 112 publications

Nuclear Targeting Dynamics of Gold Nanoclusters for Enhanced Therapy of HER2+ Breast Cancer

Nuclear Targeting Dynamics of Gold Nanoclusters for Enhanced Therapy of HER2+ Breast Cancer

Development of Chitosan and Polylactic Acid Based Methotrexate Intravitreal Micro-Implants to Treat Primary Intraocular Lymphoma: An In Vitro Study

Applications of Lipidic and Polymeric Nanoparticles for siRNA Delivery

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Nuclear Targeting Dynamics of Gold Nanoclusters for Enhanced Therapy of HER2⁺ Breast Cancer

Nuclear Targeting Dynamics of Gold Nanoclusters for Enhanced Therapy of HER2⁺ Breast Cancer