Biopolymer-Based Nanosystems for siRNA Drug Delivery to Solid Tumors including Breast Cancer

Subhan, Abdus; Torchilin, Vladimir P.

doi:10.3390/pharmaceutics15010153

Cited by 8 publications

(6 citation statements)

References 115 publications

(150 reference statements)

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“…Biocompatible biopolymers such as cyclodextrin, chitosan, and proteins have been utilized for the siRNA delivery to diseases like melanoma, lung metastasis, and breast cancer. − CD47 immunoglobulin is highly expressed in many cancer models, as CD47 and signal-regulatory protein α (SIRPα) forms a signaling complex that helps in the escape of cancerous cells from macrophage-mediated phagocytosis. Thus, targeting the CD47 selectively can lead to the inhibition of tumor growth.…”

Section: Methods Of Sirna Deliverymentioning

confidence: 99%

Emergence of Small Interfering RNA-Based Gene Drugs for Various Diseases

Kurakula,

Vaishnavi,

Sharif

et al. 2023

ACS Omega

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Small molecule, peptide, and protein-based drugs have been developed over decades to treat various diseases. The importance of gene therapy as an alternative to traditional drugs has increased after the discovery of gene-based drugs such as Gendicine for cancer and Neovasculgen for peripheral artery disease. Since then, the pharma sector is focusing on developing gene-based drugs for various diseases. After the discovery of the RNA interference (RNAi) mechanism, the development of siRNA-based gene therapy has been accelerated immensely. siRNA-based treatment for hereditary transthyretin-mediated amyloidosis (hATTR) using Onpattro and acute hepatic porphyria (AHP) by Givlaari and three more FDA-approved siRNA drugs has set up a milestone and further improved the confidence for the development of gene therapeutics for a spectrum of diseases. siRNA-based gene drugs have more advantages over other gene therapies and are under study to treat different types of diseases such as viral infections, cardiovascular diseases, cancer, and many more. However, there are a few bottlenecks to realizing the full potential of siRNA-based gene therapy. They include chemical instability, nontargeted biodistribution, undesirable innate immune responses, and off-target effects. This review provides a comprehensive view of siRNAbased gene drugs: challenges associated with siRNA delivery, their potential, and future prospects.

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Section: Methods Of Sirna Deliverymentioning

confidence: 99%

Emergence of Small Interfering RNA-Based Gene Drugs for Various Diseases

Kurakula,

Vaishnavi,

Sharif

et al. 2023

ACS Omega

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“…(3-aminoropyl)triethoxysilane (APTES), poly(α- l -lysine) (PLL), polyethylenimine (PEI), poly(ethylene glycol) (PEG), chitosan, cyclodextrin (CD) oligomers and others. APTES, PLL, PEI, chitosan are cationic polymers that entrap siRNA via electrostatic interaction and exhibit high silencing efficiency. , PEG prevents the particle growth by preventing further silica condensation on the particle surface, which thus controls particle size and also improves silica dispersibility Table shows the different silica surface modifications attempted for encapsulating siRNA.…”

Section: Tunable Silica Surface Chemistry: Functionalization/polymer ...mentioning

confidence: 99%

Ordered Mesoporous Silica Delivering siRNA as Cancer Nanotherapeutics: A Comprehensive Review

Gupta,

Choudhury,

Meena

et al. 2024

ACS Biomater. Sci. Eng.

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Nanosized mesoporous silica has emerged as a promising flexible platform delivering siRNA for cancer treatment. This ordered mesoporous nanosized silica provides attractive features of well-defined and tunable porosity, structure, high payload, and multiple functionalizations for targeted delivery and increasing biocompatibility over other polymeric nanocarriers. Moreover, it also overcomes the lacunae associated with traditional administration of drugs. Chemically modified porous silica matrix efficiently entraps siRNA molecules and prevents their enzymatic degradation and premature release. This Review discusses the synthesis of silica using the sol−gel approach and the advantages with different silica mesostructure. Herein, the factors affecting the synthesis of silica at nanometer scale, shape, porosity and nanoparticle surface modification are also highlighted to attain the desired nanostructured silica carriers. Additional emphasis is given to chemically modified silica delivering siRNA, where the silica nanoparticle surface was modified with different chemical moieties such as amine modified with (3-aminoropyl) triethoxysilane, polyethylenimine, chitosan, poly(ethylene glycol), and cyclodextrin polymer modification to attain high therapeutic loading, improved dispersibility and biocompatibility. Upon systemic administration, ordered mesoporous nanosized silica encounters blood cells, immune cells, and organs mainly of the reticuloendothelial system (RES). Thereby, biocompatibility and biodistribution of silica based nanocarriers are deliberated to design principles for smart and efficacious nanostructured silica-siRNA carriers and their clinical trial status. This Review further reports the future scopes and challenges for developing silica nanomaterial as a promising siRNA delivery vehicle demanding FDA approval.

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“…One of the extensively studied biomaterials used in nanocarriers for the oral delivery of siRNA is chitosan, a biocompatible polysaccharide [ 164 , 165 ]. It can prolong the residence time on the epithelial surface and facilitate paracellular drug transport due to its mucoadhesive and mucopermeable nature.…”

Section: Recent Challenges Of Orally Bioavailable Middle-to-large Mol...mentioning

confidence: 99%

Oral Absorption of Middle-to-Large Molecules and Its Improvement, with a Focus on New Modality Drugs

Asano,

Takakusa,

Nakai

2023

Pharmaceutics

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To meet unmet medical needs, middle-to-large molecules, including peptides and oligonucleotides, have emerged as new therapeutic modalities. Owing to their middle-to-large molecular sizes, middle-to-large molecules are not suitable for oral absorption, but there are high expectations around orally bioavailable macromolecular drugs, since oral administration is the most convenient dosing route. Therefore, extensive efforts have been made to create bioavailable middle-to-large molecules or develop absorption enhancement technology, from which some successes have recently been reported. For example, Rybelsus® tablets and Mycapssa® capsules, both of which contain absorption enhancers, were approved as oral medications for type 2 diabetes and acromegaly, respectively. The oral administration of Rybelsus and Mycapssa exposes their pharmacologically active peptides with molecular weights greater than 1000, namely, semaglutide and octreotide, respectively, into systemic circulation. Although these two medications represent major achievements in the development of orally absorbable peptide formulations, the oral bioavailability of peptides after taking Rybelsus and Mycapssa is still only around 1%. In this article, we review the approaches and recent advances of orally bioavailable middle-to-large molecules and discuss challenges for improving their oral absorption.

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Biopolymer-Based Nanosystems for siRNA Drug Delivery to Solid Tumors including Breast Cancer

Cited by 8 publications

References 115 publications

Emergence of Small Interfering RNA-Based Gene Drugs for Various Diseases

Emergence of Small Interfering RNA-Based Gene Drugs for Various Diseases

Ordered Mesoporous Silica Delivering siRNA as Cancer Nanotherapeutics: A Comprehensive Review

Oral Absorption of Middle-to-Large Molecules and Its Improvement, with a Focus on New Modality Drugs

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