Selective trafficking of light chain-conjugated nanoparticles to the kidney and renal cell carcinoma

Farideh Ordikhani; Vivek Kasinath; Mayuko Uehara; Aram Akbarzadeh; Osman A Yilmam; Li Dai; Hamza Aksu; Sungwook Jung; Liwei Jiang; Xiaofei Li; Jing Zhao; Baharak Bahmani; Takaharu Ichimura; Paolo Fiorina; Nasim Annabi; Reza Abdi

doi:10.1016/j.nantod.2020.100990

Selective trafficking of light chain-conjugated nanoparticles to the kidney and renal cell carcinoma

Farideh Ordikhani
, Vivek Kasinath
, Mayuko Uehara
, Aram Akbarzadeh
, Osman A Yilmam
, Li Dai
, Hamza Aksu
, Sungwook Jung
, Liwei Jiang
, Xiaofei Li
, Jing Zhao
, Baharak Bahmani
, Takaharu Ichimura
, Paolo Fiorina
, Nasim Annabi
, Reza Abdi

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

20 Scopus citations

Abstract

Specific delivery platforms for drugs to the kidney and diagnostic agents to renal cell carcinoma (RCC) constitute urgent but unfulfilled clinical needs. To address these challenges, we engineered nanocarriers that interact selectively for the first time with proximal tubule epithelial cells (PTECs) in the kidney and with RCC through the interplay between lambda light chains (LCs) attached to PEGylated polylactic-co-glycolic acid (PLGA) nanoparticles and the membrane protein megalin. Systemic administration of these light chain-conjugated nanoparticles (LC-NPs) to mice resulted in their specific retention by megalin-expressing PTECs for seven days. Repetitive dosing of LC-NPs demonstrated no renal toxicity. LC-NPs also localized selectively to megalin-expressing RCC tumors in mice. Moreover, we confirmed that both the primary tumor and lymph node metastases of human RCC express megalin, reinforcing the potential of LC-NPs for clinical use. Thus, LC-NPs can contribute potentially to improving the management of both non-oncologic and oncologic renal disorders.

Original language	English
Article number	100990
Journal	Nano Today
Volume	35
DOIs	https://doi.org/10.1016/j.nantod.2020.100990
State	Published - Dec 2020
Externally published	Yes

Keywords

Kidney
Light chain proteins
Megalin
Nanoparticles
Renal cell carcinoma

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10.1016/j.nantod.2020.100990

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Ordikhani, F., Kasinath, V., Uehara, M., Akbarzadeh, A., A Yilmam, O., Dai, L., Aksu, H., Jung, S., Jiang, L., Li, X., Zhao, J., Bahmani, B., Ichimura, T., Fiorina, P., Annabi, N., & Abdi, R. (2020). Selective trafficking of light chain-conjugated nanoparticles to the kidney and renal cell carcinoma. Nano Today, 35, Article 100990. https://doi.org/10.1016/j.nantod.2020.100990

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title = "Selective trafficking of light chain-conjugated nanoparticles to the kidney and renal cell carcinoma",

abstract = "Specific delivery platforms for drugs to the kidney and diagnostic agents to renal cell carcinoma (RCC) constitute urgent but unfulfilled clinical needs. To address these challenges, we engineered nanocarriers that interact selectively for the first time with proximal tubule epithelial cells (PTECs) in the kidney and with RCC through the interplay between lambda light chains (LCs) attached to PEGylated polylactic-co-glycolic acid (PLGA) nanoparticles and the membrane protein megalin. Systemic administration of these light chain-conjugated nanoparticles (LC-NPs) to mice resulted in their specific retention by megalin-expressing PTECs for seven days. Repetitive dosing of LC-NPs demonstrated no renal toxicity. LC-NPs also localized selectively to megalin-expressing RCC tumors in mice. Moreover, we confirmed that both the primary tumor and lymph node metastases of human RCC express megalin, reinforcing the potential of LC-NPs for clinical use. Thus, LC-NPs can contribute potentially to improving the management of both non-oncologic and oncologic renal disorders.",

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doi = "10.1016/j.nantod.2020.100990",

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T1 - Selective trafficking of light chain-conjugated nanoparticles to the kidney and renal cell carcinoma

AU - Ordikhani, Farideh

AU - Kasinath, Vivek

AU - Uehara, Mayuko

AU - Akbarzadeh, Aram

AU - A Yilmam, Osman

AU - Dai, Li

AU - Aksu, Hamza

AU - Jung, Sungwook

AU - Jiang, Liwei

AU - Li, Xiaofei

AU - Zhao, Jing

AU - Bahmani, Baharak

AU - Ichimura, Takaharu

AU - Fiorina, Paolo

AU - Annabi, Nasim

AU - Abdi, Reza

PY - 2020/12

Y1 - 2020/12

N2 - Specific delivery platforms for drugs to the kidney and diagnostic agents to renal cell carcinoma (RCC) constitute urgent but unfulfilled clinical needs. To address these challenges, we engineered nanocarriers that interact selectively for the first time with proximal tubule epithelial cells (PTECs) in the kidney and with RCC through the interplay between lambda light chains (LCs) attached to PEGylated polylactic-co-glycolic acid (PLGA) nanoparticles and the membrane protein megalin. Systemic administration of these light chain-conjugated nanoparticles (LC-NPs) to mice resulted in their specific retention by megalin-expressing PTECs for seven days. Repetitive dosing of LC-NPs demonstrated no renal toxicity. LC-NPs also localized selectively to megalin-expressing RCC tumors in mice. Moreover, we confirmed that both the primary tumor and lymph node metastases of human RCC express megalin, reinforcing the potential of LC-NPs for clinical use. Thus, LC-NPs can contribute potentially to improving the management of both non-oncologic and oncologic renal disorders.

AB - Specific delivery platforms for drugs to the kidney and diagnostic agents to renal cell carcinoma (RCC) constitute urgent but unfulfilled clinical needs. To address these challenges, we engineered nanocarriers that interact selectively for the first time with proximal tubule epithelial cells (PTECs) in the kidney and with RCC through the interplay between lambda light chains (LCs) attached to PEGylated polylactic-co-glycolic acid (PLGA) nanoparticles and the membrane protein megalin. Systemic administration of these light chain-conjugated nanoparticles (LC-NPs) to mice resulted in their specific retention by megalin-expressing PTECs for seven days. Repetitive dosing of LC-NPs demonstrated no renal toxicity. LC-NPs also localized selectively to megalin-expressing RCC tumors in mice. Moreover, we confirmed that both the primary tumor and lymph node metastases of human RCC express megalin, reinforcing the potential of LC-NPs for clinical use. Thus, LC-NPs can contribute potentially to improving the management of both non-oncologic and oncologic renal disorders.

KW - Kidney

KW - Light chain proteins

KW - Megalin

KW - Nanoparticles

KW - Renal cell carcinoma

UR - https://www.scopus.com/pages/publications/85096128526

U2 - 10.1016/j.nantod.2020.100990

DO - 10.1016/j.nantod.2020.100990

M3 - Article

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SN - 1748-0132

VL - 35

JO - Nano Today

JF - Nano Today

M1 - 100990

ER -

Selective trafficking of light chain-conjugated nanoparticles to the kidney and renal cell carcinoma

Abstract

Keywords

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