Novel Cyclic Peptide–Drug Conjugate P6-SN38 Toward Targeted Treatment of EGFR Overexpressed Non-Small Cell Lung Cancer DOI Creative Commons
Andrii Bazylevich, Anthony R. Miller, Irina G. Tkachenko

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(12), P. 1613 - 1613

Published: Dec. 19, 2024

Background/Objectives: Here, we report on the synthesis and biological evaluation of a novel peptide–drug conjugate, P6-SN38, which consists EGFR-specific short cyclic peptide, P6, Topo I inhibitor SN38, is bioactive metabolite anticancer drug irinotecan. Methods: SN38 attached to peptide at position 20 E ring’s tertiary hydroxyl group via mono-succinate linker. Results: The developed conjugate (PDC) exhibited sub-micromolar activity EGFR-positive (EGFR+) cell lines but no effect EGFR-negative (EGFR−) cells. In vivo studies have shown that this PDC specifically accumulates in EGFR+ non-small lung cancer (NSCLC) xenografts presents superior compared antibody cetuximab (ErbituxTM) free SN38. 10 mg/kg dose P6-SN38 side-by-side EGFR+/EGFR− xenograft shows eradication tumor with good tolerance, inhibition growth EGFR− counterpart. Conclusions: examined study was proven be highly efficient for NSCLC, broadening its utilization targeted therapy EGFR overexpressed cancers.

Language: Английский

Advance in peptide-based drug development: delivery platforms, therapeutics and vaccines DOI Creative Commons
Wen‐Jing Xiao, Wenjie Jiang, Zheng Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 5, 2025

The successful approval of peptide-based drugs can be attributed to a collaborative effort across multiple disciplines. integration novel drug design and synthesis techniques, display library technology, delivery systems, bioengineering advancements, artificial intelligence have significantly expedited the development groundbreaking drugs, effectively addressing obstacles associated with their character, such as rapid clearance degradation, necessitating subcutaneous injection leading increasing patient discomfort, ultimately advancing translational research efforts. Peptides are presently employed in management diagnosis diverse array medical conditions, diabetes mellitus, weight loss, oncology, rare diseases, additionally garnering interest facilitating targeted platforms advancement vaccines. This paper provides an overview present market clinical trial progress therapeutics, platforms, It examines key areas through literature analysis emphasizes structural modification principles well recent advancements screening, design, technologies. accelerated including peptide-drug complexes, new vaccines, innovative diagnostic reagents, has potential promote era precise customization disease therapeutic schedule.

Language: Английский

Citations

1
Hierarchically Engineered Self-Adaptive Nanoplatform Guided Intuitive and Precision Interventions for Deep-Seated Glioblastoma DOI
Wei Cheng,

Haijing Qu,

Jiaojiao Yang

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Glioblastoma multiforme (GBM), particularly the deep-seated tumor where surgical removal is not feasible, poses great challenges for clinical treatments due to complicated biological barriers and risk of damaging healthy brain tissue. Here, we hierarchically engineer a self-adaptive nanoplatform (SAN) that overcomes delivery by dynamically adjusting its structure, surface charge, particle size, targeting moieties precisely distinguish between parenchyma cells. We further devise

Language: Английский

Citations

0
Nanotherapy of Glioblastoma—Where Hope Grows DOI Open Access
Jan Grzegorzewski, Maciej Michalak,

Maria Wołoszczuk

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 1814 - 1814

Published: Feb. 20, 2025

Localization in the central nervous system, diffuse growth, presence of stem cells, and numerous resistance mechanisms, all make glioblastoma (GBM) an incurable tumor. The standard treatment GBM consisting surgery; radio- chemotherapy with temozolomide provides insufficient therapeutic benefit needs to be updated effective modern solutions. One most promising intensively explored approaches against is use nanotherapy. first, so far only, nanoparticle-based therapy approved for NanoThermTM. It based on iron oxide nanoparticles thermal ablation tumor a magnetic field. Numerous other types nanotherapies are being evaluated, including polymer lipid-based nanoformulations, nanodiscs, dendrimers, metallic, silica, or bioderived nanoparticles, among others. advantages these nanoscale drug carriers include improved penetration across blood-brain barrier, targeted delivery, biocompatibility, lower systemic toxicity, while major problems their implementation involve scaling up production high costs. Nevertheless, taking impressive benefits into consideration, it seems obvious that combined effort scientific world will need taken tackle challenges implement novel therapies clinics, giving hope battle can finally won.

Language: Английский

Citations

0
Targeted Delivery of Nanoparticle-Conveyed Neutrophils to the Glioblastoma Site for Efficient Therapy DOI

Chunxian Piao,

Jaeho Lee, G. E. Kim

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: 16(32), P. 41819 - 41827

Published: July 26, 2024

Glioblastoma is a common brain tumor that poses considerable challenges in drug delivery. In this study, we investigated the potential of cell-based nanoparticles for targeted delivery to glioblastoma sites. The anticancer temozolomide (TMZ)-loaded T7-cholesterol nanoparticle micelles efficiently delivered neutrophils and, subsequently, tumors. T7 cell-penetrating peptide enhances T7/TMZ target cells. also serves as transferrin peptide, enabling T7-conjugated cholesterol can self-assemble into aqueous solution and attach membrane neutrophils. We confirmed were located inside Thereafter, T7/TMZ-conveyed administered mouse model, penetrate blood-brain barrier deliver drugs directly site. evaluated efficiency therapeutic effects intravenous injection model. These results demonstrate promising role neutrophil-based systems therapy glioblastoma.

Language: Английский

Citations

2
Recent Progress in the Development of Peptide-Drug Conjugates (PDCs) for Cancer Therapy DOI

Haiqi He,

Xin Deng, Zhijie Wang

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 284, P. 117204 - 117204

Published: Dec. 24, 2024

Language: Английский

Citations

1
Targeted delivery of SN38 to breast cancer using amphiphilic diblock copolymers PHPMA-b-PBAEM as micellar carriers with AS1411 aptamer DOI Creative Commons

Rozita Feizpour,

Atena Jabbari, Farzin Hadizadeh

et al.

International Journal of Pharmaceutics, Journal Year: 2024, Volume and Issue: 661, P. 124387 - 124387

Published: June 24, 2024

Breast cancer treatment can be challenging, but a targeted drug delivery system (DDS) has the potential to make it more effective and reduce side effects. This study presents novel nanotherapeutic DDS developed through self-assembly of an amphiphilic di-block copolymer deliver chemotherapy SN38 specifically breast cells. The vehicle was constructed from PHPMA-b-PEAMA diblock synthesized via RAFT polymerization. A single emulsion method then used encapsulate within nanoparticles (NPs) formed copolymer. AS1411 DNA aptamer covalently bonded surface micellar NPs, producing DDS. Molecular dynamics (MD) simulation studies were also performed on di block polymeric system, demonstrating that interacted well with block. in vitro results demonstrated AS1411- decorated SN38-loaded HPMA NPs highly toxic cells while having minimal effect non-cancerous Remarkably, vivo elucidated ability enhance antitumor SN38, suppressing tumor growth improving survival rates compared free SN38.

Language: Английский

Citations

0
Novel Cyclic Peptide–Drug Conjugate P6-SN38 Toward Targeted Treatment of EGFR Overexpressed Non-Small Cell Lung Cancer DOI Creative Commons
Andrii Bazylevich, Anthony R. Miller, Irina G. Tkachenko

et al.

Pharmaceutics, Journal Year: 2024, Volume and Issue: 16(12), P. 1613 - 1613

Published: Dec. 19, 2024

Background/Objectives: Here, we report on the synthesis and biological evaluation of a novel peptide–drug conjugate, P6-SN38, which consists EGFR-specific short cyclic peptide, P6, Topo I inhibitor SN38, is bioactive metabolite anticancer drug irinotecan. Methods: SN38 attached to peptide at position 20 E ring’s tertiary hydroxyl group via mono-succinate linker. Results: The developed conjugate (PDC) exhibited sub-micromolar activity EGFR-positive (EGFR+) cell lines but no effect EGFR-negative (EGFR−) cells. In vivo studies have shown that this PDC specifically accumulates in EGFR+ non-small lung cancer (NSCLC) xenografts presents superior compared antibody cetuximab (ErbituxTM) free SN38. 10 mg/kg dose P6-SN38 side-by-side EGFR+/EGFR− xenograft shows eradication tumor with good tolerance, inhibition growth EGFR− counterpart. Conclusions: examined study was proven be highly efficient for NSCLC, broadening its utilization targeted therapy EGFR overexpressed cancers.

Language: Английский

Citations

0