Synergistic nanotherapy systems and methods of use thereof

Patent metadata

Field	Value
Publication number	US-11260128-B2
Application number	US-201715852598-A
Country	US
Kind code	B2
Filing date	Dec 22, 2017
Priority date	Jun 22, 2015
Publication date	Mar 1, 2022
Grant date	Mar 1, 2022

Abstract

The presently disclosed subject matter is directed to a method of treating cancer, such as (but not limited to) metastatic bladder and breast cancer. The disclosed method comprises using two treatment modalities to synergistically treat primary and secondary tumor cells in a subject. The first element of the method comprises administering a therapeutically effective amount of a plasmonics-active metal nanoparticle to a subject comprising a primary cancer and a distant metastatic site, wherein the nanoparticle concentrates at the primary cancer. The method further comprises exposing the subject to photon radiation at the site of the primary cancer. The second element of the disclosed method comprises administering a therapeutically effective amount of an immune checkpoint modulator to the subject. The synergistic combination provides a rapid, safe, and effective treatment of local and distant lesions, better than each modality alone.

First claim

What is claimed is:

1. A method of treating primary tumors and metastatic cancer sites comprising:
administering a therapeutically effective amount of plasmonics-active gold nanostars and a therapeutically effective amount of an anti-PD-L1 antibody to a subject with a primary tumor and a distant metastatic site, wherein the nanostar concentrates at the primary tumor and the distant metastatic site; and
inducing hyperthermia, ablation, or both at a site of the primary tumor with laser radiation, wherein the plasmonics-active gold nanostars absorb the laser radiation and produce a localized photothermal therapy,
wherein the combination of the anti-PD-L1 antibody and the localized photothermal therapy results in damage to cells of the primary tumor and damage to cells at the distant metastatic site to treat the cancer;
wherein the cancer is selected from breast cancer and bladder cancer.

2. The method of claim 1 , wherein the anti-PD-L1 antibody targets a costimulatory molecule selected from the group consisting of PD-1, PD-L1, CTLA-4, LAG3, B7-DC, ICOS, ICOSL, HVEM, LGIHT, CD40, CD40L, 4-1BB, 4-1BBL, OX40, OX40L, GITR, GITRL, TIM1, TIM3, TIM4, CD70, CD27, CD30, CD30L, BTLA4, TREM2, GM-CSF, and combinations thereof.

3. The method of claim 1 , wherein the plasmonic-active gold nanostars have a plasmon peak ranging from about 600 nm to about 1000 nm.

4. The method of claim 3 , wherein the plasmonics-active gold nanostars have a mean tip-to-tip diameter from 10-200 nm.

5. The method of claim 1 , wherein the administering of the plasmonics-active gold nanostars is systemically by intravenous injection, by direct injection at the primary cancer site, by oral delivery, by adsorption, by deposition, or by combinations thereof.

Assignees

• Univ Duke

Inventors

• Vo-Dinh Tuan
• Inman Brant A
• Maccarini Paolo
• Palmer Greg
• Liu Yang
• Weitzel Douglas

Classifications

• B22F1/0545

  Dispersions or suspensions of nanosized particles · CPC title

• A61N5/062

  Photodynamic therapy, i.e. excitation of an agent · CPC title

• A61N5/00

  Radiation therapy (ultrasound therapy A61N7/00; devices or apparatus applicable to both therapy and diagnosis A61B6/00) · CPC title

• A61K33/242 Primary

  Gold; Compounds thereof · CPC title

• A61P35/04

  specific for metastasis · CPC title