Mitochondria-Targeted Cassic Acid Base Nanoprodrug for Enhanced Anti-Inflammatory and Osteogenic Effects in Osteoarthritis

CATPCS prodrug-based nanodrug delivery system (PNDDS), a mitochondria-targeted nanoprodrug combining Cassic acid (CA) with a PEG-modified chitosan-tripolyphosphate (TPP) molecule (CATPCS), overcomes the limitations of free Cassic acid in treating osteoarthritis (OA) and bone regeneration. FTIR and DLS confirm that lyophilized CATPCS self-assembles into stable, homogeneous spherical nanoparticles (230.8 ± 45.5 nm, PDI: 0.180, ζ potential: 30.5 ± 9.2 mV). For targeted delivery, HR-TEM scans verified this spherical morphology. In vitro studies show that IL-1β-stimulated chondrocytes internalize and colocalize CATPCS more effectively than free CA and CA NPs owing to the positively charged TPP moiety. CATPCS and CA NPs have in vitro cytotoxicity lower than that of free CA, indicating biocompatibility. In IL-1β-stimulated chondrocytes, CATPCS significantly reduced the level of ROS and RNS, increased cartilage-specific markers (COL2A1, ACAN), and lowered inflammatory factors. Increased levels of alkaline phosphatase (ALP) and alizarin red staining (ARS) protected mitochondrial membrane potential, reduced chondrocyte apoptosis, and increased osteogenesis. Comparable to Diclofenac (DG), CATPCS decreased mechanical allodynia, cold hypersensitivity, and thermal hyperalgesia in MIA-induced OA rats. CATPCS reduced oxidative stress by lowering MDA and restoring SOD and GPx activity according to biochemical studies. Histopathology demonstrated that CATPCS reduced inflammation and preserved the OA animals’ articular cartilage thickness. Mitochondrial-targeted CATPCS PNDDS is an excellent osteoarthritis and bone regeneration therapy because of its enhanced delivery, anti-inflammatory, antioxidant, and osteogenic effects.

• Publication year

  2025

• Venue

  ACS Omega

• Publication date

  2025-08-11

• Fields of study

  Medicine, Materials Science

• Identifiers
  DOI 10.1021/acsomega.5c03216PMID 40852312PMCID 12368642
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Development of self-assembled (+)-Nootkatone delivery system using Gliadin-Carboxymethyl chitosan composite nanoparticles: Fabrication, characterization, and pharmaceutical application.

  2025cited by this paper
• Chitosan Nanoparticles: Approaches to Preparation, Key Properties, Drug Delivery Systems, and Developments in Therapeutic Efficacy

  2025cited by this paper
• CEA-Functionalized Gold Nanoparticles as a Nanovaccine Platform: In Vitro Evaluation of Cytocompatibility, Cellular Uptake, and Antigen Processing

  2025cited by this paper
• Ameliorative effects of undifferentiated and differentiated BM-MSCs in MIA-induced osteoarthritic Wistar rats: roles of NF-κB and MMPs signaling pathways.

  2024cited by this paper
• Mitochondrial quality control dysfunction in osteoarthritis: Mechanisms, therapeutic strategies & future prospects.

  2024cited by this paper
• Construction of mitochondrial-targeting nano-prodrug for enhanced Rhein delivery and treatment for osteoarthritis in vitro.

  2024cited by this paper
• E3 ubiquitin ligases: key regulators of osteogenesis and potential therapeutic targets for bone disorders

  2024cited by this paper
• Cartilage Integrity: A Review of Mechanical and Frictional Properties and Repair Approaches in Osteoarthritis

  2024cited by this paper
• Development and Characterization of Polylactic Acid (PLA)-Based Nanocomposites Used for Food Packaging

  2023cited by this paper
• The Multifaceted Role of Jasmonic Acid in Plant Stress Mitigation: An Overview

  2023cited by this paper
• Enhancing Therapeutic Efficacy of Curcumin: Advances in Delivery Systems and Clinical Applications

  2023cited by this paper
• Cytotoxicity and Antibiofilm Activity of Silver-Polypropylene Nanocomposites

  2023cited by this paper
• Cost Effectiveness of Pharmacological Management for Osteoarthritis: A Systematic Review

  2022cited by this paper
• Cartilage tissue engineering: From proinflammatory and anti-inflammatory cytokines to osteoarthritis treatments

  2022cited by this paper
• The Implication of Reactive Oxygen Species and Antioxidants in Knee Osteoarthritis

  2021cited by this paper
• Chitosan Nanoparticles at the Biological Interface: Implications for Drug Delivery

  2021cited by this paper
• Monosodium iodoacetate-induced subchondral bone microstructure and inflammatory changes in an animal model of osteoarthritis

  2021cited by this paper
• S-Equol Protects Chondrocytes against Sodium Nitroprusside-Caused Matrix Loss and Apoptosis through Activating PI3K/Akt Pathway

  2021cited by this paper
• Subchondral Bone Remodeling: A Therapeutic Target for Osteoarthritis

  2021cited by this paper
• Targeting the Opening of Mitochondrial Permeability Transition Pores Potentiates Nanoparticle Drug Delivery and Mitigates Cancer Metastasis

  2020cited by this paper
• PLGA nanoparticle preparations by emulsification and nanoprecipitation techniques: effects of formulation parameters

  2020cited by this paper
• Subcutaneous tanezumab for osteoarthritis of the hip or knee: efficacy and safety results from a 24-week randomised phase III study with a 24-week follow-up period

  2020cited by this paper
• Validation of an FT-IR microscopy method for the determination of microplastic particles in surface waters

  2020cited by this paper
• Reactive Oxygen Species-Related Nanoparticle Toxicity in the Biomedical Field

  2020cited by this paper
• Pathogenesis of Osteoarthritis: Risk Factors, Regulatory Pathways in Chondrocytes, and Experimental Models

  2020cited by this paper
• Effects of Starch Incorporation on the Physicochemical Properties and Release Kinetics of Alginate-Based 3D Hydrogel Patches for Topical Delivery

  2020cited by this paper
• Biomedical Applications of Reactive Oxygen Species Generation by Metal Nanoparticles

  2020cited by this paper
• Polymer-coated nanoparticles and their effects on mitochondrial function in brain endothelial cells.

  2019cited by this paper
• Antimicrobial peptide LL-37 is bactericidal against Staphylococcus aureus biofilms

  2019cited by this paper
• Highly Biocompatible Chlorin e6-Loaded Chitosan Nanoparticles for Improved Photodynamic Cancer Therapy.

  2018cited by this paper
• The Immunomodulatory and Anti-Inflammatory Role of Polyphenols

  2018cited by this paper
• The effect of particle shape on cellular interaction and drug delivery applications of micro- and nanoparticles.

  2017cited by this paper
• Understanding knee osteoarthritis from the patients’ perspective: a qualitative study

  2017cited by this paper
• Design of polyaspartic acid peptide-poly (ethylene glycol)-poly (ε-caprolactone) nanoparticles as a carrier of hydrophobic drugs targeting cancer metastasized to bone

  2017cited by this paper
• Methods Used to Evaluate Pain Behaviors in Rodents

  2017cited by this paper
• Mitochondria-targeted drug delivery system for cancer treatment

  2016cited by this paper
• Mitochondria targeting nano agents in cancer therapeutics

  2016cited by this paper
• Pharmacological Properties of Protocatechuic Acid and Its Potential Roles as Complementary Medicine

  2015cited by this paper
• Dual-responsive polymer coated superparamagnetic nanoparticle for targeted drug delivery and hyperthermia treatment.

  2015cited by this paper
• The epidemiology of osteoarthritis.

  2014cited by this paper
• Improving effects of chitosan nanofiber scaffolds on osteoblast proliferation and maturation

  2014cited by this paper
• Subchondral bone in osteoarthritis: insight into risk factors and microstructural changes

  2013cited by this paper
• Effects of Particle Size and Surface Modification on Cellular Uptake and Biodistribution of Polymeric Nanoparticles for Drug Delivery

  2013cited by this paper
• Evaluating the antioxidant capacity of natural products: a review on chemical and cellular-based assays.

  2013cited by this paper
• Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis

  2012cited by this paper
• Biocompatibility of chitosan-coated iron oxide nanoparticles with osteoblast cells

  2012cited by this paper
• Acceleration of osteogenic differentiation of preosteoblastic cells by chitosan containing nanofibrous scaffolds.

  2009cited by this paper
• Grading of monosodium iodoacetate-induced osteoarthritis reveals a concentration-dependent sensitization of nociceptors in the knee joint of the rat.

  2009cited by this paper
• Cationic polystyrene nanosphere toxicity depends on cell-specific endocytic and mitochondrial injury pathways.

  2008cited by this paper
• Quantitation of mitochondrial alterations associated with apoptosis.

  2002cited by this paper

• No citing papers are available for this paper.