Background: Osteoarthritis (OA) is a progressive joint disorder marked by the degradation of cartilage. Elevated concentrations of hypoxia-inducible factor-2 alpha (HIF-2 alpha) are intricately linked to the pathological development of OA. PT2385 has demonstrated effective inhibition of HIF-2 alpha, thereby potentially impeding the initial advancement of OA. Nevertheless, challenges persist, including limited penetration into the deeper layers of cartilage, issues related to charge rejection, and a heightened rate of clearance from the joint. These constraints necessitate further consideration and exploration. Methods: It has been demonstrated that PT2385 exhibits efficient inhibition of HIF-2 alpha expression, thereby contributing to the delay in the progression of osteoarthritis. The pH-responsive attributes of carbon quantum dots, specifically those employing m-phenylenediamine (m-CQDs) coated with bovine serum albumin (BSA), have been systematically evaluated. In both in vitro settings involving cartilage explants and in vivo experiments, the efficacy of BSA-m-CQDs-PT2385 (BCP) has been confirmed in facilitating the transport of PT2385 to the middle and deep layers of cartilage. Furthermore, the BCP system demonstrates controlled drug release contingent upon alterations in environmental pH. Results: While the use of PT2385 alone provides protective effects on chondrocytes within an inflamed environment, there exists an opportunity for further enhancement in its efficacy when administered via intra-articular injection. The BCP formulation, characterized by appropriate particle size and charge, facilitates seamless penetration into cartilage tissue. Additionally, BCP demonstrates the capability to release drugs in response to changes in environmental pH. In vitro experiments reveal that BCP effectively inhibits Hif-2 alpha expression and catabolic factors in chondrocytes. Notably, cartilage explants and in vivo experiments indicate that BCP surpasses PT2385 alone in inhibiting the expression of HIF-2 alpha and matrix metalloproteinase 13, particularly in the middle and deep layers. Conclusions: The BCP drug delivery system exhibits selective release of PT2385 in response to pH changes occurring during the progression of osteoarthritis (OA), thereby inhibiting HIF-2 alpha expression deep within the cartilage. The use of BCP significantly augments the capacity of PT2385 to retard both cartilage degeneration and the progression of osteoarthritis. Consequently, BCP as an innovative approach utilizing m-CQDs to deliver PT2385 into articular cartilage, shows potential for treating osteoarthritis. This strategy opens new avenues for osteoarthritis treatment.