A kNGR Peptide-Tethered Lipid–Polymer Hybrid Nanocarrier-Based Synergistic Approach for Effective Tumor Therapy: Development, Characterization, Ex-Vivo, and In-Vivo Assessment

Madhu Gupta; Vikas Sharma; Kalicharan Sharma; Anoop Kumar; Ajay Sharma; Imran Kazmi; Fahad A. Al-Abbasi; Sami I. Alzarea; Obaid Afzal; Abdulmalik Saleh Alfawaz Altamimi; Sachin Kumar Singh; Gaurav Gupta; Keshav Raj Paudel; Philip M. Hansbro; Kamal Dua

doi:10.3390/pharmaceutics14071401

A kNGR Peptide-Tethered Lipid–Polymer Hybrid Nanocarrier-Based Synergistic Approach for Effective Tumor Therapy: Development, Characterization, Ex-Vivo, and In-Vivo Assessment

Madhu Gupta
, Vikas Sharma
, Kalicharan Sharma
, Anoop Kumar
, Ajay Sharma
, Imran Kazmi
, Fahad A. Al-Abbasi
, Sami I. Alzarea
, Obaid Afzal
, Abdulmalik Saleh Alfawaz Altamimi
, Sachin Kumar Singh
, Gaurav Gupta
, Keshav Raj Paudel
, Philip M. Hansbro
, Kamal Dua

Pharmaceutical Chemistry

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

The present study aims to design, develop and characterize kNGR (Asn-Gly-Arg) peptide-conjugated lipid–polymer-based nanoparticles for the target-specific delivery of anticancer bioactive(s), i.e., Paclitaxel (PTX). The kNGR-PEG-DSPE conjugate was synthesized and characterized by using spectral analysis. The dual-targeted PLGA–lecithin–PEG core-shell nanoparticles (PLNs-kNGR-NPs) were synthesized using a modified nanoprecipitation process, and their physiological properties were determined. The results support that, compared to other NPs, PLNs-kNGR-NPs are highly cytotoxic, owing to higher apoptosis and intracellular uptake. The significance of rational nanoparticle design for synergistic treatment is shown by the higher tumor volume inhibition percentage rate (59.7%), compared to other designed formulations in Balb/c mice in the HT-1080 tumor-induced model. The overall results indicate that the PLNs-kNGR-NPs-based hybrid lipid–polymer nanoparticles present the highest therapeutic efficacy against solid tumor overexpressing the CD13 receptors.

Original language	English
Article number	1401
Journal	Pharmaceutics
Volume	14
Issue number	7
DOIs	https://doi.org/10.3390/pharmaceutics14071401
State	Published - Jul 2022

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

hybrid nanoparticles
intracellular delivery
kNGR peptide
polymer–lipid CD13 receptor
targeted therapy

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10.3390/pharmaceutics14071401

Cite this

Gupta, M., Sharma, V., Sharma, K., Kumar, A., Sharma, A., Kazmi, I., Al-Abbasi, F. A., Alzarea, S. I., Afzal, O., Altamimi, A. S. A., Singh, S. K., Gupta, G., Paudel, K. R., Hansbro, P. M., & Dua, K. (2022). A kNGR Peptide-Tethered Lipid–Polymer Hybrid Nanocarrier-Based Synergistic Approach for Effective Tumor Therapy: Development, Characterization, Ex-Vivo, and In-Vivo Assessment. Pharmaceutics, 14(7), Article 1401. https://doi.org/10.3390/pharmaceutics14071401

@article{f330fccdc61242338994b6f490173ac4,

title = "A kNGR Peptide-Tethered Lipid–Polymer Hybrid Nanocarrier-Based Synergistic Approach for Effective Tumor Therapy: Development, Characterization, Ex-Vivo, and In-Vivo Assessment",

abstract = "The present study aims to design, develop and characterize kNGR (Asn-Gly-Arg) peptide-conjugated lipid–polymer-based nanoparticles for the target-specific delivery of anticancer bioactive(s), i.e., Paclitaxel (PTX). The kNGR-PEG-DSPE conjugate was synthesized and characterized by using spectral analysis. The dual-targeted PLGA–lecithin–PEG core-shell nanoparticles (PLNs-kNGR-NPs) were synthesized using a modified nanoprecipitation process, and their physiological properties were determined. The results support that, compared to other NPs, PLNs-kNGR-NPs are highly cytotoxic, owing to higher apoptosis and intracellular uptake. The significance of rational nanoparticle design for synergistic treatment is shown by the higher tumor volume inhibition percentage rate (59.7\%), compared to other designed formulations in Balb/c mice in the HT-1080 tumor-induced model. The overall results indicate that the PLNs-kNGR-NPs-based hybrid lipid–polymer nanoparticles present the highest therapeutic efficacy against solid tumor overexpressing the CD13 receptors.",

keywords = "hybrid nanoparticles, intracellular delivery, kNGR peptide, polymer–lipid CD13 receptor, targeted therapy",

author = "Madhu Gupta and Vikas Sharma and Kalicharan Sharma and Anoop Kumar and Ajay Sharma and Imran Kazmi and Al-Abbasi, \{Fahad A.\} and Alzarea, \{Sami I.\} and Obaid Afzal and Altamimi, \{Abdulmalik Saleh Alfawaz\} and Singh, \{Sachin Kumar\} and Gaurav Gupta and Paudel, \{Keshav Raj\} and Hansbro, \{Philip M.\} and Kamal Dua",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = jul,

doi = "10.3390/pharmaceutics14071401",

language = "English",

volume = "14",

journal = "Pharmaceutics",

issn = "1999-4923",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "7",

}

Gupta, M, Sharma, V, Sharma, K, Kumar, A, Sharma, A, Kazmi, I, Al-Abbasi, FA, Alzarea, SI, Afzal, O , Altamimi, ASA, Singh, SK, Gupta, G, Paudel, KR, Hansbro, PM & Dua, K 2022, 'A kNGR Peptide-Tethered Lipid–Polymer Hybrid Nanocarrier-Based Synergistic Approach for Effective Tumor Therapy: Development, Characterization, Ex-Vivo, and In-Vivo Assessment', Pharmaceutics, vol. 14, no. 7, 1401. https://doi.org/10.3390/pharmaceutics14071401

TY - JOUR

T1 - A kNGR Peptide-Tethered Lipid–Polymer Hybrid Nanocarrier-Based Synergistic Approach for Effective Tumor Therapy

T2 - Development, Characterization, Ex-Vivo, and In-Vivo Assessment

AU - Gupta, Madhu

AU - Sharma, Vikas

AU - Sharma, Kalicharan

AU - Kumar, Anoop

AU - Sharma, Ajay

AU - Kazmi, Imran

AU - Al-Abbasi, Fahad A.

AU - Alzarea, Sami I.

AU - Afzal, Obaid

AU - Altamimi, Abdulmalik Saleh Alfawaz

AU - Singh, Sachin Kumar

AU - Gupta, Gaurav

AU - Paudel, Keshav Raj

AU - Hansbro, Philip M.

AU - Dua, Kamal

PY - 2022/7

Y1 - 2022/7

N2 - The present study aims to design, develop and characterize kNGR (Asn-Gly-Arg) peptide-conjugated lipid–polymer-based nanoparticles for the target-specific delivery of anticancer bioactive(s), i.e., Paclitaxel (PTX). The kNGR-PEG-DSPE conjugate was synthesized and characterized by using spectral analysis. The dual-targeted PLGA–lecithin–PEG core-shell nanoparticles (PLNs-kNGR-NPs) were synthesized using a modified nanoprecipitation process, and their physiological properties were determined. The results support that, compared to other NPs, PLNs-kNGR-NPs are highly cytotoxic, owing to higher apoptosis and intracellular uptake. The significance of rational nanoparticle design for synergistic treatment is shown by the higher tumor volume inhibition percentage rate (59.7%), compared to other designed formulations in Balb/c mice in the HT-1080 tumor-induced model. The overall results indicate that the PLNs-kNGR-NPs-based hybrid lipid–polymer nanoparticles present the highest therapeutic efficacy against solid tumor overexpressing the CD13 receptors.

AB - The present study aims to design, develop and characterize kNGR (Asn-Gly-Arg) peptide-conjugated lipid–polymer-based nanoparticles for the target-specific delivery of anticancer bioactive(s), i.e., Paclitaxel (PTX). The kNGR-PEG-DSPE conjugate was synthesized and characterized by using spectral analysis. The dual-targeted PLGA–lecithin–PEG core-shell nanoparticles (PLNs-kNGR-NPs) were synthesized using a modified nanoprecipitation process, and their physiological properties were determined. The results support that, compared to other NPs, PLNs-kNGR-NPs are highly cytotoxic, owing to higher apoptosis and intracellular uptake. The significance of rational nanoparticle design for synergistic treatment is shown by the higher tumor volume inhibition percentage rate (59.7%), compared to other designed formulations in Balb/c mice in the HT-1080 tumor-induced model. The overall results indicate that the PLNs-kNGR-NPs-based hybrid lipid–polymer nanoparticles present the highest therapeutic efficacy against solid tumor overexpressing the CD13 receptors.

KW - hybrid nanoparticles

KW - intracellular delivery

KW - kNGR peptide

KW - polymer–lipid CD13 receptor

KW - targeted therapy

UR - https://www.scopus.com/pages/publications/85133681717

U2 - 10.3390/pharmaceutics14071401

DO - 10.3390/pharmaceutics14071401

M3 - Article

AN - SCOPUS:85133681717

SN - 1999-4923

VL - 14

JO - Pharmaceutics

JF - Pharmaceutics

IS - 7

M1 - 1401

ER -

A kNGR Peptide-Tethered Lipid–Polymer Hybrid Nanocarrier-Based Synergistic Approach for Effective Tumor Therapy: Development, Characterization, Ex-Vivo, and In-Vivo Assessment

Abstract

UN SDGs

Keywords

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