The University of Texas System

University of Illinois

Case Western Reserve University

Massachusetts Institute of Technology

Northwest A&f University

Jinming Gao

David A Boothman

Baran D Sumer

Yiguang Wang

Kejin Zhou

Xinpeng Ma

Gang Huang

Xiaonan Huang

Yang Li

Tian Zhao

Paul Joseph Hergenrother

Joseph S Bair

Elizabeth I Parkinson

Lifen Cao

Zachary R Moore

Xiumei Huang

Xiuquan Luo

Erik Bey

Robert Samuel Langer

Jeffrey L Duerk

Jonathan S Lewin

Zhijian Chen

Qi Wei

Chris Flask

Yang-Xin Fu

Brent Weinberg

John Pink

Laura E Niklason

Lanfang Huang

Hua Wang

Ping Xiang

Zhaoyuan Bian

Jiangjiang Tang

Bo Ren

Tongyi Huang

Qiang Feng

Min Luo

Haocheng Cai

Xu Wang

Houliang Tang

Jonathan Wilhelm

Yinjian Zhou

David Boothman

Zhaohui Wang

Ying Dong

Wei Li

Suxin Li

Hua Ai

Xintao Shuai

Yuliang Liu

Norased Nasongkla

The present disclosure relates to degradable polymers which contain a hydrophobic and hydrophilic segment which is sensitive to pH. In some aspects, the polymers form a micelle which is sensitive to pH and have backbones which are capable of undergoing degradation in vivo. In some aspects, the disclosure also provides methods of using these degradable polymers for the delivery of a drug.

Biodegradable ultra-pH sensitive polymers

Provided herein are block copolymers comprising a hydrophilic polymer segment and a hydrophobic polymer segment, wherein the hydrophilic polymer segment comprises a polymer selected from the group consisting of: poly(ethylene oxide) (PEO), poly(methacrylate phosphatidyl choline) (MPC), and polyvinylpyrrolidone (PVP), wherein the hydrophobic polymer segment comprises wherein R' is —H or —CH, wherein R is —NRR, wherein Rand Rare alkyl groups, wherein Rand Rare the same or different, wherein Rand Rtogether have from 5 to 16 carbons, wherein Rand Rmay optionally join to form a ring, wherein n is 1 to about 10, and wherein x is about 20 to about 200 in total. Also provided are pH-sensitive micelle compositions for therapeutic and diagnostic applications.

Block copolymer and micelle compositions and methods of use thereof

Described herein are therapeutic pH responsive compositions useful for the treatment of cancer. The compositions involve combining a STING activating polymer micelle, such as PC7A, with a non-peptide STING agonist, such as cGAMP. Methods of administering these compositions in the treatment of cancer are also disclosed. These methods include administration of the pharmaceutical compositions by intratumoral injection in the treatment of solid tumors.

Polyvalent sting activating compositions and uses thereof

Described herein are therapeutic pH responsive compositions comprising a block copolymer and a therapeutic agent useful for the treatment of cancer.

PH responsive block copolymer compositions and micelles that inhibit MCT 1 and related proteins

The present disclosure relates to polymers which contain a hydrophobic and hydrophilic segment which is sensitive to pH. In some aspects, the polymers form a micelle which is sensitive to pH and results in a change in fluorescence based upon the particular pH. In some aspects, the disclosure also provides methods of using the polymers for the imaging of cellular or extracellular environment or delivering a drug.

Library of pH responsive polymers and nanoprobes thereof

Disclosed are 3,4-methylenedioxyphenylimidazolylethanonexime ether derivatives, a preparation method and use thereof, and a drug for the treatment of Alzheimer's disease, which relates to the technical field of preparation of acetophenone oxime ether compounds. The (Z)-3,4-methylenedioxyphenylimidazolylethanonexime ether derivatives provided by the present disclosure show a significant effect on the inhibition of NO production, with an ECof 2.07-5.41 &#x3bc;mol/L. Compared with the positive control group of quercetin (with an ECof 9.56 &#x3bc;mol/L) and oxiconazole (with an ECof 13.5 &#x3bc;mol/L), the inhibitory effect is stronger without significant cytotoxicity (cell viability &#x3e;90%), which can be used to prepare drugs for the treatment of Alzheimer's disease.

3,4-methylenedioxyphenylimidazolylethanonexime ether derivative, preparation method and use thereof, and drug for the treatment of Alzheimer's disease

In some aspects, the present disclosure provides vaccine compositions comprising an antigen and a diblock copolymer wherein the diblock copolymer is pH responsive. In some embodiments, these compositions activate the STING and/or the interferon receptor pathways. In some embodiments, the diblock copolymer hits a pKa from about 6 to about 7.5. Also provided herein are methods of treatment using these compositions to treat an infectious disease or cancer.

Sting activating nanovaccine for immunotherapy

Provided herein are block copolymers comprising a hydrophilic polymer segment and a hydrophobic polymer segment, wherein the hydrophilic polymer segment comprises a polymer selected from the group consisting of: poly(ethylene oxide) (PEO), poly(methacrylate phosphatidyl choline) (MPC), and polyvinylpyrrolidone (PVP), wherein the hydrophobic polymer segment comprises wherein R' is &#x2014;H or &#x2014;CH, wherein R is &#x2014;NRR, wherein Rand Rare alkyl groups, wherein Rand Rare the same or different, wherein Rand Rtogether have from 5 to 16 carbons, wherein Rand Rmay optionally join to form a ring, wherein n is 1 to about 10, and wherein x is about 20 to about 200 in total. Also provided are pH-sensitive micelle compositions for therapeutic and diagnostic applications.

Provided herein are naphthoquinones compounds such as those with a hydrogen bond donating group of the formula (I): wherein: R, R, R, R, R, and n are as defined herein. Also provided herein are pharmaceutical composition of the present compounds and methods of treatment using the compounds including their use in the treatment of cancer. 

Naphthoquinones, pro-drugs, and methods of use thereof

The therapies described herein can be selectively lethal toward a variety of different cancer cell types and cancer conditions in a subject. The combination therapies described herein can be useful for the management, treatment, control, or adjunct treatment of diseases, where the selective legality is beneficial in chemotherapeutic therapy, particularly where the disease is accompanied by elevated levels of NQO1.

Tumor-selective combination therapy

The therapies described herein can be selectively lethal toward a variety of different cancer cell types and cancer conditions in a subject. The combination therapies described herein can be useful for the management, treatment, control, or adjunct treatment of diseases, where the selective lethality is beneficial in chemotherapeutic therapy, particularly where the disease is accompanied by elevated levels of NQO1.

The present invention relates to pH-tunable, highly activatable multicolored fluorescent nanoplatforms and methods of using the nanoplatforms in a variety of applications including, but not limited to, investigating fundamental cell physiological processes such as pH regulation in endocytic vesicles, endosome/lysosome maturation, and effect of pH on receptor cycling and trafficking of subcellular organelles.

Multicolored pH-activatable fluorescence nanoplatform

Growing community of inventors

Plano, TX, United States of America

Jinming Gao