Amphiphilic Block Copolymer Nanostructures as a Tunable Delivery Platform: Perspective and Framework for the Future Drug Product Development DOI
Gaurav Sinsinbar, Anivind Kaur Bindra, Shaoqiong Liu

et al.

Biomacromolecules, Journal Year: 2024, Volume and Issue: 25(2), P. 541 - 563

Published: Jan. 19, 2024

Nanoformulation of active payloads or pharmaceutical ingredients (APIs) has always been an area interest to achieve targeted, sustained, and efficacious delivery. Various delivery platforms have explored, but loading APIs challenging because the chemical structural properties these molecules. Polymersomes made from amphiphilic block copolymers (ABCPs) shown enormous promise as a tunable API platform confer multifold advantages over lipid-based systems. For example, COVID booster vaccine comprising polymersomes encapsulating spike protein (ACM-001) recently completed Phase I clinical trial provides case for developing safe drug products based on ABCP platforms. However, several limitations need be resolved before they can reach their full potential. In this Perspective, we would like highlight such aspects requiring further development translating ABCP-based proof concept viable commercial product.

Language: Английский

Biomedical Metal–Organic Framework Materials: Perspectives and Challenges DOI Creative Commons
Alec Wang,

Madeline Walden,

Romy Ettlinger

et al.

Advanced Functional Materials, Journal Year: 2023, Volume and Issue: 34(43)

Published: Nov. 21, 2023

Abstract Metal–organic framework (MOF) materials are gaining significant interest in biomedical research, owing to their high porosity, crystallinity, and structural compositional diversity. Their versatile hybrid organic/inorganic chemistry endows MOFs with the capacity retain organic (drug) molecules, metals, gases, effectively channel electrons photons, survive harsh physiological conditions such as low pH, even protect sensitive biomolecules. Extensive preclinical research has been carried out treat several pathologies and, recently, integration other stents implants demonstrated promising performance regenerative medicine. However, there remains a gap between MOF translation into clinically societally relevant medicinal products. Here, intrinsic features of outlined suitability specific applications detoxification, drug gas delivery, or (combination) therapy platforms is discussed. Furthermore, examples how have engineered evaluated different medical indications, including cancer, microbial, inflammatory diseases described. Finally, challenges facing clinic critically examined, goal establishing directions more realistic approaches that can bridge translational MOF‐containing (nano)materials.

Language: Английский

Citations

52
Wound healing strategies based on nanoparticles incorporated in hydrogel wound patches DOI Creative Commons
Paulami Dam, Merve Celik, Merve Ustun

et al.

RSC Advances, Journal Year: 2023, Volume and Issue: 13(31), P. 21345 - 21364

Published: Jan. 1, 2023

Nanoparticle-modified hydrogels exhibit substantial promise in the realm of wound healing, with their ability to expedite tissue regeneration, mitigate infection risks, and facilitate enhanced therapeutic outcomes.

Language: Английский

Citations

51
Chemically Modified Platforms for Better RNA Therapeutics DOI

Yesi Shi,

Xueyan Zhen,

Yiming Zhang

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(3), P. 929 - 1033

Published: Jan. 29, 2024

RNA-based therapies have catalyzed a revolutionary transformation in the biomedical landscape, offering unprecedented potential disease prevention and treatment. However, despite their remarkable achievements, these encounter substantial challenges including low stability, susceptibility to degradation by nucleases, prominent negative charge, thereby hindering further development. Chemically modified platforms emerged as strategic innovation, focusing on precise alterations either RNA moieties or associated delivery vectors. This comprehensive review delves into platforms, underscoring significance augmenting performance translational prospects of therapeutics. It encompasses an in-depth analysis various chemically that been instrumental propelling therapeutics toward clinical utility. Moreover, scrutinizes rationale behind diverse chemical modification techniques aiming at optimizing therapeutic efficacy molecules, facilitating robust management. Recent empirical studies corroborating enhancement through modifications are highlighted. Conclusively, we offer profound insights transformative impact drugs delineates prospective trajectories for future development integration.

Language: Английский

Citations

51
Spleen SORT LNP Generated in situ CAR T Cells Extend Survival in a Mouse Model of Lymphoreplete B Cell Lymphoma DOI Creative Commons
Ester Álvarez‐Benedicto, Zeru Tian, Sumanta Chatterjee

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(44)

Published: Aug. 31, 2023

Abstract Chimeric Antigen Receptor (CAR) T cell immunotherapy is revolutionizing treatment for patients suffering from B‐cell lymphoma (BL). However, the current method of CAR production complicated and expensive, requiring collection patient blood to enrich population, ex vivo engineering/activation, quality assessment before can receive treatment. Herein we leverage Spleen Selective ORgan Targeted (SORT) Lipid Nanoparticles (LNPs) produce cells in situ bypass extensive laborious process currently used. Optimized SORT LNPs containing 10 % 18 : 1 PA transfected CD3+, CD8+, CD4+ wild‐type mice. delivered Cre recombinase mRNA encoding reporter mice a lymphoreplete B model (respectively) after intravenous injection without need active targeting ligands. Moreover, increased overall survival with less aggressive form lymphoma. In addition, reduced tumor metastasis liver by increasing infiltrating lymphocytes. Overall, these results offer promising alternative pre‐clinical potential treat hematological malignancies.

Language: Английский

Citations

48
Reformulating lipid nanoparticles for organ-targeted mRNA accumulation and translation DOI Creative Commons
Kexin Su, Lu Shi, Tao Sheng

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 5, 2024

Abstract Fully targeted mRNA therapeutics necessitate simultaneous organ-specific accumulation and effective translation. Despite some progress, delivery systems are still unable to fully achieve this. Here, we reformulate lipid nanoparticles (LNPs) through adjustments in material structures compositions systematically the pulmonary hepatic (respectively) distribution expression. A combinatorial library of degradable-core based ionizable cationic lipids is designed, following by optimisation LNP compositions. Contrary current paradigms, our findings demonstrate that cholesterol phospholipid dispensable for functionality. Specifically, cholesterol-removal addresses persistent challenge preventing nanoparticle tissues. By modulating simplifying intrinsic components, concurrent translation achieved lung liver, respectively. This targeting strategy applicable existing with potential expand progress precise therapy diverse diseases.

Language: Английский

Citations

47
High-throughput barcoding of nanoparticles identifies cationic, degradable lipid-like materials for mRNA delivery to the lungs in female preclinical models DOI Creative Commons
Lulu Xue, Alex G. Hamilton, Gan Zhao

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 29, 2024

Abstract Lipid nanoparticles for delivering mRNA therapeutics hold immense promise the treatment of a wide range lung-associated diseases. However, lack effective methodologies capable identifying pulmonary delivery profile chemically distinct lipid libraries poses significant obstacle to advancement therapeutics. Here we report implementation barcoded high-throughput screening system as means identify lung-targeting efficacy cationic, degradable lipid-like materials. We combinatorially synthesize 180 lipids which are initially screened in vitro. then use barcoding technology quantify how selected 96 deliver DNA barcodes vivo. The top-performing nanoparticle formulation Cas9-based genetic editors exhibits therapeutic potential antiangiogenic cancer therapy within lung tumor model female mice. These data demonstrate that employing tool with tropism holds development next-generation extrahepatic platforms.

Language: Английский

Citations

45
In vivo editing of lung stem cells for durable gene correction in mice DOI
Yehui Sun, Sumanta Chatterjee,

Xizhen Lian

et al.

Science, Journal Year: 2024, Volume and Issue: 384(6701), P. 1196 - 1202

Published: June 13, 2024

In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of in cells, yielding responses. Intravenously administered gene-editing LNPs activatable tdTomato mice achieved >70% lung editing, sustaining expression >80% epithelial cells 660 days. Addressing cystic fibrosis (CF), NG-ABE8e messenger RNA (mRNA)-sgR553X mediated >95% transmembrane conductance regulator (CFTR) DNA correction, restored CFTR function primary patient-derived bronchial equivalent to Trikafta F508del, corrected intestinal organoids and R553X nonsense mutations 50% CF mice. These findings introduce LNP-enabled tissue disease-modifying correction.

Language: Английский

Citations

45
Nanomedicine-based co-delivery of a calcium channel inhibitor and a small molecule targeting CD47 for lung cancer immunotherapy DOI Creative Commons
Yuedong Guo, Qunqun Bao, Ping Hu

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 11, 2023

Pro-tumoral macrophages in lung tumors present a significant challenge immunotherapy. Here, we introduce pH-responsive nanomedicine approach for activating anti-tumoral and dendritic cells. Using layered double hydroxide nanosheet carrier, co-deliver T-type calcium channel inhibitor (TTA-Q6) CD47 (RRX-001) into tumors. In the tumor acidic environment, TTA-Q6 is released, disrupting cancer cell uptake, causing endoplasmic reticulum stress inducing calreticulin transfer to surface. Surface activates triggers maturation, promoting effective antigen presentation therefore antitumor T Simultaneously, RRX-001 reduces protein levels, aiding preventing immune escape by calreticulin-rich models male mice, this combined shows anti-tumor effects immunity against re-exposure, highlighting its potential

Language: Английский

Citations

43
Bone-marrow-homing lipid nanoparticles for genome editing in diseased and malignant haematopoietic stem cells DOI

Xizhen Lian,

Sumanta Chatterjee, Yehui Sun

et al.

Nature Nanotechnology, Journal Year: 2024, Volume and Issue: 19(9), P. 1409 - 1417

Published: May 23, 2024

Language: Английский

Citations

31
Advances and applications of nanoparticles in cancer therapy DOI Creative Commons

Xianzhou Huang,

Tao He, Xiuqi Liang

et al.

MedComm – Oncology, Journal Year: 2024, Volume and Issue: 3(1)

Published: March 1, 2024

Abstract Rapid growth in nanoparticles (NPs) as delivery systems holds vast promise to promote therapeutic approaches for cancer treatment. Presently, a diverse array of NPs with unique properties have been developed overcome different challenges and achieve sophisticated routes enhancement series therapies. Inspiring advances achieved the field therapy using NPs. In this review, we aim summarize up‐to‐date progression addressing various challenges, expect elicit novel potential opportunities alternatively. We first introduce sorts NP technologies, illustrate their mechanisms, present applications. Then, achievements made by break obstacles delivering cargoes specific sites through particular are highlighted, including long‐circulation, tumor targeting, responsive release, subcellular localization. subsequently retrospect recent research treatments from single therapy, like chemotherapy, combination chemoradiotherapy, integrative therapy. Finally, perspectives impact on oncology discussed. believe review can offer deeper understanding

Language: Английский

Citations

28