Targeted Nanoparticles for Cancer Therapy

Blanco, María Dolores Valdueza; Teijón, César; Olmo, Rosa; Teijón, José M.

doi:10.5772/51382

Cited by 19 publications

(8 citation statements)

References 177 publications

(198 reference statements)

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“…Passive delivery exemplifies to the nanocarrier mediated delivery of therapeutics within the tumor through their permeable vasculature primarily by passive diffusion, whereas active targeting refers to the delivery to a targeted site based on molecular recognition. , In passive targeting (Figure ), nanoparticles take the benefit of the leaky tumor vasculature and preferentially accumulate within the perivascular tumor environment due to enhanced permeability and retention (EPR) effect . As apoptosis mechanism is deregulated in cancerous cells, they uncontrollably divide and proliferate by gaining energy or nutrition abnormally from the surrounding blood vessels and thus forming wide and leaky blood vessels around the cells induced by neoangiogenesis.…”

Section: Introductionmentioning

confidence: 99%

Precision Cancer Nanotherapy: Evolving Role of Multifunctional Nanoparticles for Cancer Active Targeting

et al. 2019

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Nanoparticles with multifunctionality are being designed and formulated to overcome various limitations of drugs as well as conventional drug delivery systems. Engineered nanoparticles to specifically target cancer cells have the ability to reduce collateral damage on normal tissue due to pan-toxic effects of drugs. Pragmatic approaches are in consideration to make advancement in cancer therapy as the new developed methods exhibited an improved targeted anticancer therapeutic delivery with better treatment outcomes. An effective cancer therapy requires both the passive and active targeting, along with a consistent knowledge of various physiologic barriers to successfully achieve targeted delivery. The nanoparticles can be linked with tumor targeting moieties like specific ligands, monoclonal antibodies, and carbohydrates for active targeting of cancer cells with great affinity and precision. This review presents some recent research on targeted delivery for cancer therapy and also discusses examples of types of engineered nanoparticles exploited for active cancer targeting.

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Section: Introductionmentioning

confidence: 99%

Precision Cancer Nanotherapy: Evolving Role of Multifunctional Nanoparticles for Cancer Active Targeting

et al. 2019

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“…Of note, a variety of other (multifunctional) nanoscale platinum drug delivery devices have been developed. ,, Although we did not test other nanoformulations experimentally, it is expected that they may also be useful to eradicate LRRC8A-based cisplatin-resistant cells, although their cellular uptake and biocompatibility need to be examined. Likewise, multifunctional nanotools, allowing for codeliveries of drugs with siRNAs for specific gene silencing, have been designed in the past, as an approach to increase the power of nanoformulations by targeting proteins, which contribute to cisplatin resistance due to their overexpression. − We though demonstrated that low LRRC8A levels are key for cisplatin resistance, and thus, the codelivery of LRRC8A gene silencing siRNA would rather increase instead of breaking resistance and, thus, seems not applicable for our target.…”

Section: Resultsmentioning

confidence: 94%

“…The rapid progress in nanotechnology combined with our increased knowledge of the complex cross-talk at nanobio interfaces has raised high expectations in nanomedicine to also combat cancer, including therapy resistances. − Numerous delivery and theranostic nanotools have been developed to date, often claiming to be superior to small molecule chemotherapeutics due to sustained drug release, better cancer cell uptake, enhanced permeation and retention (EPR) effect in tumors, prolonged bioavailability, and less side-effects. − Impressive developments also include the design of multifunctional nanotools, allowing codeliveries of drugs with siRNAs or peptides as well as the addition of active tumor cell targeting decoys, such as antibodies, aptamers, or peptides onto the NPs’ surfaces. − Moreover, NPs have been reported to better kill resistant cancer cells through enhanced cell internalization, stimuli-responsive drug release, inhibition of drug efflux, and more. However, postulated effects have not always been investigated sufficiently or understood mechanistically and multifunctional nanotools have not reached the clinic yet …”

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confidence: 99%

Targeting Cancer Chemotherapy Resistance by Precision Medicine-Driven Nanoparticle-Formulated Cisplatin

et al. 2021

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Therapy resistance is the major cause of cancer death. As patients respond heterogeneously, precision/personalized medicine needs to be considered, including the application of nanoparticles (NPs). The success of therapeutic NPs requires to first identify clinically relevant resistance mechanisms and to define key players, followed by a rational design of biocompatible NPs capable to target resistance. Consequently, we employed a tiered experimental pipeline from in silico to analytical and in vitro to overcome cisplatin resistance. First, we generated cisplatin-resistant cancer cells and used next-generation sequencing together with CRISPR/Cas9 knockout technology to identify the ion channel LRRC8A as a critical component for cisplatin resistance. LRRC8A’s cisplatin-specificity was verified by testing free as well as nanoformulated paclitaxel or doxorubicin. The clinical relevance of LRRC8A was demonstrated by its differential expression in a cohort of 500 head and neck cancer patients, correlating with patient survival under cisplatin therapy. To overcome LRRC8A-mediated cisplatin resistance, we constructed cisplatin-loaded, polysarcosine-based core cross-linked polymeric NPs (NPCis, Ø ∼ 28 nm) with good colloidal stability, biocompatibility (low immunogenicity, low toxicity, prolonged in vivo circulation, no complement activation, no plasma protein aggregation), and low corona formation properties. 2D/3D-spheroid cell models were employed to demonstrate that, in contrast to standard of care cisplatin, NPCis significantly (p < 0.001) eradicated all cisplatin-resistant cells by circumventing the LRRC8A-transport pathway via the endocytic delivery route. We here identified LRRC8A as critical for cisplatin resistance and suggest LRRC8A-guided patient stratification for ongoing or prospective clinical studies assessing therapy resistance to nanoscale platinum drug nanoformulations versus current standard of care formulations.

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“…The conjugation of different molecules to the nanoparticles permitted their use in a wider range of application fields and equipped them with new properties, aimed at a specific recognition of cell types (like tumor cells) or tissues. The commonly used classification of targeting moieties is shown in Table 2 [56][57][58][59][60]. Table 2 Classification of targeting molecules used for nanoparticle functionalization.…”

Section: Targeting Moleculesmentioning

confidence: 99%

Biological targeting with nanoparticles: state of the art

Kozlova

Epple

2013

BioNanoMaterials

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Nanoparticles are used in medicine to deliver drugs, for imaging, for vaccination and for local heating of tissue (tumor thermotherapy). If malignant tissue shall be addressed, it is of prime importance to direct the nanoparticles to their target. This can be accomplished by making use of physical effects (e.g., the EPR effect: enhanced permeation and retention) or by chemical modification of the nanoparticles to specifically recognize cells or tissues. The efficiency of the targeting can be assessed by in vitro cell culture experiments and also in vivo in animal experiments. As they are closest to the practical clinical application, in vivo imaging methods are particularly suitable to monitor the targeting. In general, a limited colloid-chemical stability of the nanoparticles in a biological environment and the formation of a protein corona around the nanoparticle may constrain their targeting ability. The current state of such targeting strategies is reviewed and discussed.

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Targeted Nanoparticles for Cancer Therapy

Cited by 19 publications

References 177 publications

Precision Cancer Nanotherapy: Evolving Role of Multifunctional Nanoparticles for Cancer Active Targeting

Precision Cancer Nanotherapy: Evolving Role of Multifunctional Nanoparticles for Cancer Active Targeting

Targeting Cancer Chemotherapy Resistance by Precision Medicine-Driven Nanoparticle-Formulated Cisplatin

Biological targeting with nanoparticles: state of the art

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