pH-sensitive polymeric micelles for targeted delivery to inflamed joints

Luo

Macromolecular Bioscience

et al. 2018

Carbonic anhydrase IX (CA IX), over‐expressed on cancer cells, catalyzes CO2 to bicarbonate and protons, contributing to the acidic extracellular pH (pHe), which enhances the multidrug resistance of tumor cells. Therefore, alleviating tumor acidosis would greatly improve the outcome of chemotherapy. This work fabricates acetazolamide (ACE)‐loaded pH‐responsive nanoparticles (ACE‐NPs), which are quickly disintegrated in an acidic solution (pH 6.8), resulting in a quick release of ACE from these NPs to inhibit the expression of CA IX, thus up‐regulating the pHe value. These ACE‐NPs have no obvious in vitro cytotoxicity and in vivo studies confirm the accumulation of ACE‐NPs in tumor tissue. In addition, mice treated with ACE and paclitaxel (PTX) co‐loaded NPs show a smaller tumor size and a higher survival rate when compared to that of mice treated with ACE‐ or PTX‐loaded NPs. This work reveals that simultaneous delivery of ACE and chemotherapy agents to tumor tissue can up‐regulate the acidic pHe value, consequently enhancing the anti‐tumor ability of chemotherapy medicine. These findings open a new window for enhancing the anti‐tumor ability of traditional chemotherapy in clinic.

Section: Resultsmentioning

confidence: 99%

Section: Characterization Of Phpp Copolymers and Phpp Npsmentioning

confidence: 99%

Acetazolamide‐Loaded pH‐Responsive Nanoparticles Alleviating Tumor Acidosis to Enhance Chemotherapy Effects

Luo

Macromolecular Bioscience

et al. 2018

“…The reason may be due to the instability in OA synovial uid and the lacking of controlled drug release kinetics according to the severity of OA. The previous studies showed that in amed-joint is marked by weakly acidic environment (may down to 6.0) during the process of cartilage degradation [10][11][12][13], providing a suitable trigger to drug control release. In order to stably deliver drug into OA-affected site without undesired drug early leakage and increase treatment effect by controlled release the drug to in amed chondrocytes, it is necessary to develop a smart pH-stimuli-responsive drug control release system for precisely treating of OA.…”

Section: Introductionmentioning

confidence: 99%

pH-responsive and hyaluronic acid-functionalized metal-organic frameworks for therapy of osteoarthritis

Xiong

Qin

Chen

et al. 2020

Preprint

Drug therapy of osteoarthritis (OA) is limited by the short retention and lacking of stimulus-responsiveness after intra-articular (IA) injection. The weak acid microenvironment in joint provides a potential trigger for controlled drug release systems in the treatment of OA. Herein, we developed an pH-responsive metal−organic frameworks (MOFs) system modified by hyaluronic acid (HA) and loaded with an anti-inflammatory protocatechuic acid (PCA), designated as MOF@HA@PCA, for the therapy of OA. Results demonstrated that MOF@HA@PCA could smartly respond to acidic conditions in OA microenvironment and gradually release PCA, which could remarkably reduce synovial inflammation in both IL-1β induced chondrocytes and the OA joints. MOF@HA@PCA also down-regulated the expression of inflammatory markers of OA and promoted the expression of cartilage-specific makers. This work may provide a new insight for the design of efficient nanoprobes for precision theranostics of OA.

“…Signi cant efforts have focused on engineering drug delivery systems to prolong the retention time of drug in the joint [5,6]. In recent years, emerging stimulusresponsive smart systems for targeted imaging and precision therapy have attracted increasing interest, such as pH [7,8], ROS [9] or NO [10] triggered drug release systems upon exposure to in ammation tissues, which not only prolonged drug release, but also increased speci city to tissue and cells. The selection of optimal stimulus for the smart drug delivery system is the key for OA therapy.…”

Section: Introductionmentioning

confidence: 99%

MMP-13 Enzyme and pH Responsive Theranostic Nanoplatform for Osteoarthritis

Lan

Chen

Pang

et al. 2020

Preprint

Stimulus-responsive therapy permits precise control of therapeutic effect only at lesion of interest, which determines it a promising method for diagnosis and imaging-guided precision therapy. The acid environment and overexpressed matrix metalloproteinases-13 (MMP-13) are typical markers in osteoarthritis (OA), which enables the development of stimulus-responsive drug delivery system with high specificity for OA. We herein demonstrate a nano-micelle based stimuli-responsive theranostic strategy with reporting and drug release controlled by acidic PH and MMP-13 for OA therapy. Such nanoplatform is incorporated with a motif specifically targeting on cartilage, a motif responsive to matrix metalloproteinases-13 to specifically report OA condition and biodynamics of nano-micelles, an anti-inflammatory drug (e.g., psoralidin (PSO)) from traditional Chinese medicine, and a biocompatible polymeric skeleton for sustainable drug release in response to the acidic OA condition. The high effectiveness of this targeted precision therapy is demonstrated comprehensively by both in vitro and vivo evidences.