A photothermal driven chemotherapy for the treatment of metastatic melanoma

Himanshu N. Bhatt; Rimpy Diwan; Edgar A. Borrego; Carlos Alberto Martínez Pérez; Armando Varela-Ramirez; Raj Kumar; Renato J. Aguilera; Md Nurunnabi

doi:10.1016/j.jconrel.2023.08.005

A photothermal driven chemotherapy for the treatment of metastatic melanoma

Himanshu N. Bhatt, Rimpy Diwan, Edgar A. Borrego, Carlos Alberto Martínez Pérez, Armando Varela-Ramirez, Raj Kumar, Renato J. Aguilera, Md Nurunnabi

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

4 Scopus citations

Abstract

Solid tumors are abnormal mass of tissue, which affects the organs based on its malignancy and leads to the dysfunction of the affected organs. The major problem associated with treatment of solid tumors is delivering anticancer therapeutics to the deepest layers/core of the solid tumor. Deposition of excessive extracellular matrix (ECM) hinders the therapeutics to travel towards the core of the tumor. Therefore, conventional anticancer therapeutics can only reduce the tumor size and that also for a limited duration, and tumor recurrence occurs once the therapy is discontinued. Additionally, by the time the cancer is diagnosed, the cancer cells already started affecting the major organs of the body such as lung, liver, spleen, kidney, and brain, due to their ability to metastasize and lung is the primary site for them to be infiltrated. To facilitate the anticancer therapeutics to penetrate the deeper layers of tumor, and to provide concurrent treatment of both the solid tumor and metastasis, we have designed and developed a Bimodal Light Assisted Skin Tumor and Metastasis Treatment (BLAST), which is a combination of photothermal and chemotherapeutic moieties. The BLAST is composed of 2D boron nitride (BN) nanosheet with adsorbed molecules of BCL-2 inhibitor, Navitoclax (NAVI) on its surface, that can breakdown excessive ECM network and thereby facilitate dissociation of the solid tumor. The developed BLAST was evaluated for its ability to penetrate solid tumors using 3D spheroids for the uptake, cytotoxicity, growth inhibition, reactive oxygen species (ROS) detection, penetration, and downregulation of proteins upon laser irradiation. The in vivo therapeutic studies on a skin cancer mice model revealed that the BLAST with and without laser were able to penetrate the solid tumor, reduce tumor volume in mice, dissociate the protein network, and prevent lung metastasis as confirmed by immunohistochemistry and western blot analysis. Post analysis of serum and blood components revealed the safety and efficacy of BLAST in mice. Hence, the developed BLAST holds strong promise in solid tumor treatment and metastasis prevention simultaneously.

Original language	English
Pages (from-to)	314-333
Number of pages	20
Journal	Journal of Controlled Release
Volume	361
DOIs	https://doi.org/10.1016/j.jconrel.2023.08.005
State	Published - Sep 2023
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2023 Elsevier B.V.

Funding

We acknowledge funding by Cancer Prevention Research Institute of Texas (CPRIT) through Texas Regional Excellence in Cancer Award (TREC) under Award No. PR210153, and National Institutes of Health (NIH) under Award No R03OD032624. We also acknowledge the funding received by a Research Centers at Minority Institutions (RCMI) grant funded by the National Institute on Minority Health and Health Disparities (NIMHD), a component of the National Institutes of Health under Award No. 5G12MD00759 and U54MD007592 to the Border Biomedical Research Center (BBRC) at the University of Texas at El Paso (UTEP). We thank the staff of the Cellular Characterization and Biorepository (CCB) Core Facility for the services and facilities provided by grant 8G12MD007592 to the Border Biomedical Research Center (BBRC) from the National Institute on Minority Health and Health Disparities. The graphical abstract and Fig. 7A were created using BioRender.com. The contents of this paper are solely the authors' responsibility and do not necessarily represent the official views of NIH, RCMI, CPRIT, TREC, BBRC, and UTEP. We acknowledge funding by Cancer Prevention Research Institute of Texas (CPRIT) through Texas Regional Excellence in Cancer Award (TREC) under Award No. PR210153 , and National Institutes of Health (NIH) under Award No R03OD032624 . We also acknowledge the funding received by a Research Centers at Minority Institutions (RCMI) grant funded by the National Institute on Minority Health and Health Disparities (NIMHD), a component of the National Institutes of Health under Award No. 5G12MD00759 and U54MD007592 to the Border Biomedical Research Center (BBRC) at the University of Texas at El Paso (UTEP). We thank the staff of the Cellular Characterization and Biorepository (CCB) Core Facility for the services and facilities provided by grant 8G12MD007592 to the Border Biomedical Research Center (BBRC) from the National Institute on Minority Health and Health Disparities . The graphical abstract and Fig. 7 A were created using BioRender.com . The contents of this paper are solely the authors' responsibility and do not necessarily represent the official views of NIH, RCMI, CPRIT, TREC, BBRC, and UTEP.

Funders	Funder number
Border Biomedical Research Center
Texas Regional Excellence in Cancer Award	PR210153
National Institutes of Health	R03OD032624
Cancer Prevention and Research Institute of Texas
National Institute on Minority Health and Health Disparities	U54MD007592, 5G12MD00759
University of Texas at El Paso	8G12MD007592

Keywords

2D nanomaterials
Boron nitride
Photothermal
Solid tumor
Tumor microenvironment

UN SDGs

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

Access to Document

10.1016/j.jconrel.2023.08.005

Cite this

@article{701f5f9afd484dbdb9a57249800bdc1b,

title = "A photothermal driven chemotherapy for the treatment of metastatic melanoma",

abstract = "Solid tumors are abnormal mass of tissue, which affects the organs based on its malignancy and leads to the dysfunction of the affected organs. The major problem associated with treatment of solid tumors is delivering anticancer therapeutics to the deepest layers/core of the solid tumor. Deposition of excessive extracellular matrix (ECM) hinders the therapeutics to travel towards the core of the tumor. Therefore, conventional anticancer therapeutics can only reduce the tumor size and that also for a limited duration, and tumor recurrence occurs once the therapy is discontinued. Additionally, by the time the cancer is diagnosed, the cancer cells already started affecting the major organs of the body such as lung, liver, spleen, kidney, and brain, due to their ability to metastasize and lung is the primary site for them to be infiltrated. To facilitate the anticancer therapeutics to penetrate the deeper layers of tumor, and to provide concurrent treatment of both the solid tumor and metastasis, we have designed and developed a Bimodal Light Assisted Skin Tumor and Metastasis Treatment (BLAST), which is a combination of photothermal and chemotherapeutic moieties. The BLAST is composed of 2D boron nitride (BN) nanosheet with adsorbed molecules of BCL-2 inhibitor, Navitoclax (NAVI) on its surface, that can breakdown excessive ECM network and thereby facilitate dissociation of the solid tumor. The developed BLAST was evaluated for its ability to penetrate solid tumors using 3D spheroids for the uptake, cytotoxicity, growth inhibition, reactive oxygen species (ROS) detection, penetration, and downregulation of proteins upon laser irradiation. The in vivo therapeutic studies on a skin cancer mice model revealed that the BLAST with and without laser were able to penetrate the solid tumor, reduce tumor volume in mice, dissociate the protein network, and prevent lung metastasis as confirmed by immunohistochemistry and western blot analysis. Post analysis of serum and blood components revealed the safety and efficacy of BLAST in mice. Hence, the developed BLAST holds strong promise in solid tumor treatment and metastasis prevention simultaneously.",

keywords = "2D nanomaterials, Boron nitride, Photothermal, Solid tumor, Tumor microenvironment",

author = "Bhatt, {Himanshu N.} and Rimpy Diwan and Borrego, {Edgar A.} and P{\'e}rez, {Carlos Alberto Mart{\'i}nez} and Armando Varela-Ramirez and Raj Kumar and Aguilera, {Renato J.} and Md Nurunnabi",

note = "Publisher Copyright: {\textcopyright} 2023 Elsevier B.V.",

year = "2023",

month = sep,

doi = "10.1016/j.jconrel.2023.08.005",

language = "אנגלית",

volume = "361",

pages = "314--333",

journal = "Journal of Controlled Release",

issn = "0168-3659",

publisher = "Elsevier B.V.",

}

TY - JOUR

T1 - A photothermal driven chemotherapy for the treatment of metastatic melanoma

AU - Bhatt, Himanshu N.

AU - Diwan, Rimpy

AU - Borrego, Edgar A.

AU - Pérez, Carlos Alberto Martínez

AU - Varela-Ramirez, Armando

AU - Kumar, Raj

AU - Aguilera, Renato J.

AU - Nurunnabi, Md

PY - 2023/9

Y1 - 2023/9

N2 - Solid tumors are abnormal mass of tissue, which affects the organs based on its malignancy and leads to the dysfunction of the affected organs. The major problem associated with treatment of solid tumors is delivering anticancer therapeutics to the deepest layers/core of the solid tumor. Deposition of excessive extracellular matrix (ECM) hinders the therapeutics to travel towards the core of the tumor. Therefore, conventional anticancer therapeutics can only reduce the tumor size and that also for a limited duration, and tumor recurrence occurs once the therapy is discontinued. Additionally, by the time the cancer is diagnosed, the cancer cells already started affecting the major organs of the body such as lung, liver, spleen, kidney, and brain, due to their ability to metastasize and lung is the primary site for them to be infiltrated. To facilitate the anticancer therapeutics to penetrate the deeper layers of tumor, and to provide concurrent treatment of both the solid tumor and metastasis, we have designed and developed a Bimodal Light Assisted Skin Tumor and Metastasis Treatment (BLAST), which is a combination of photothermal and chemotherapeutic moieties. The BLAST is composed of 2D boron nitride (BN) nanosheet with adsorbed molecules of BCL-2 inhibitor, Navitoclax (NAVI) on its surface, that can breakdown excessive ECM network and thereby facilitate dissociation of the solid tumor. The developed BLAST was evaluated for its ability to penetrate solid tumors using 3D spheroids for the uptake, cytotoxicity, growth inhibition, reactive oxygen species (ROS) detection, penetration, and downregulation of proteins upon laser irradiation. The in vivo therapeutic studies on a skin cancer mice model revealed that the BLAST with and without laser were able to penetrate the solid tumor, reduce tumor volume in mice, dissociate the protein network, and prevent lung metastasis as confirmed by immunohistochemistry and western blot analysis. Post analysis of serum and blood components revealed the safety and efficacy of BLAST in mice. Hence, the developed BLAST holds strong promise in solid tumor treatment and metastasis prevention simultaneously.

AB - Solid tumors are abnormal mass of tissue, which affects the organs based on its malignancy and leads to the dysfunction of the affected organs. The major problem associated with treatment of solid tumors is delivering anticancer therapeutics to the deepest layers/core of the solid tumor. Deposition of excessive extracellular matrix (ECM) hinders the therapeutics to travel towards the core of the tumor. Therefore, conventional anticancer therapeutics can only reduce the tumor size and that also for a limited duration, and tumor recurrence occurs once the therapy is discontinued. Additionally, by the time the cancer is diagnosed, the cancer cells already started affecting the major organs of the body such as lung, liver, spleen, kidney, and brain, due to their ability to metastasize and lung is the primary site for them to be infiltrated. To facilitate the anticancer therapeutics to penetrate the deeper layers of tumor, and to provide concurrent treatment of both the solid tumor and metastasis, we have designed and developed a Bimodal Light Assisted Skin Tumor and Metastasis Treatment (BLAST), which is a combination of photothermal and chemotherapeutic moieties. The BLAST is composed of 2D boron nitride (BN) nanosheet with adsorbed molecules of BCL-2 inhibitor, Navitoclax (NAVI) on its surface, that can breakdown excessive ECM network and thereby facilitate dissociation of the solid tumor. The developed BLAST was evaluated for its ability to penetrate solid tumors using 3D spheroids for the uptake, cytotoxicity, growth inhibition, reactive oxygen species (ROS) detection, penetration, and downregulation of proteins upon laser irradiation. The in vivo therapeutic studies on a skin cancer mice model revealed that the BLAST with and without laser were able to penetrate the solid tumor, reduce tumor volume in mice, dissociate the protein network, and prevent lung metastasis as confirmed by immunohistochemistry and western blot analysis. Post analysis of serum and blood components revealed the safety and efficacy of BLAST in mice. Hence, the developed BLAST holds strong promise in solid tumor treatment and metastasis prevention simultaneously.

KW - 2D nanomaterials

KW - Boron nitride

KW - Photothermal

KW - Solid tumor

KW - Tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=85167448089&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2023.08.005

DO - 10.1016/j.jconrel.2023.08.005

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 37562554

AN - SCOPUS:85167448089

SN - 0168-3659

VL - 361

SP - 314

EP - 333

JO - Journal of Controlled Release

JF - Journal of Controlled Release

ER -

A photothermal driven chemotherapy for the treatment of metastatic melanoma

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this