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Cartilage-targeting peptide-modified dual-drug delivery nanoplatform with NIR laser response for osteoarthritis therapy.

ABSTRACT: Cartilage-targeting delivery of therapeutic agents is still an effective strategy for osteoarthritis (OA) therapy. Recently, scavenging for reactive oxygen species (ROS) and activating autophagy have been increasingly reported to treat OA effectively. In this study, we designed, for the first time, a dual-drug delivery system based on metal organic framework (MOF)-decorated mesoporous polydopamine (MPDA) which composed of rapamycin (Rap) loaded into the mesopores and bilirubin (Br) loaded onto the shell of MOF. The collagen II-targeting peptide (WYRGRL) was then conjugated on the surface of above nanocarrier to develop a cartilage-targeting dual-drug delivery nanoplatform (RB@MPMW). Our results indicated the sequential release of two agents from RB@MPMW could be achieved via near-infrared (NIR) laser irritation. Briefly, the rapid release of Br from the MOF shell exhibited excellent ROS scavenging ability and anti-apoptosis effects, however responsively reduced autophagy activity, to a certain extent. Meanwhile, following the NIR irradiation, Rap was rapidly released from MPDA core and further enhanced autophagy activation and chondrocyte protection. RB@MPMW continuously phosphorylated AMPK and further rescued mitochondrial energy metabolism of chondrocytes following IL-1? stimulation via activating SIRT1-PGC-1? signaling pathway. Additionally, the cartilage-targeting property of peptide-modified nanocarrier could be monitored via Magnetic Resonance (MR) and IVIS imaging. More significantly, RB@MPMW effectively delayed cartilage degeneration in ACLT rat model. Overall, our findings indicated that the as-prepared dual-drug delivery nanoplatform exerted potent anti-inflammation and anti-apoptotic effects, rescued energy metabolism of chondrocytes in vitro and prevented cartilage degeneration in vivo, which thereby showed positive performance for OA therapy.

SUBMITTER: Xue S

PROVIDER: S-EPMC7844135 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Cartilage-targeting peptide-modified dual-drug delivery nanoplatform with NIR laser response for osteoarthritis therapy.

Xue Song S Zhou Xiaojun X Sang Weilin W Wang Cong C Lu Haiming H Xu Yiming Y Zhong Yiming Y Zhu Libo L He Chuanglong C Ma Jinzhong J

Bioactive materials 20210126 8

Cartilage-targeting delivery of therapeutic agents is still an effective strategy for osteoarthritis (OA) therapy. Recently, scavenging for reactive oxygen species (ROS) and activating autophagy have been increasingly reported to treat OA effectively. In this study, we designed, for the first time, a dual-drug delivery system based on metal organic framework (MOF)-decorated mesoporous polydopamine (MPDA) which composed of rapamycin (Rap) loaded into the mesopores and bilirubin (Br) loaded onto t ...[more]

PMID: 33553822

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Project description:Background Knee osteoarthritis (OA) presented with knee pain and limitation of mobility is common, and it may become a chronic problem resulting in major loss of function, with related impaired activity of daily living. Current traditional therapy for knee OA includes pharmacological treatment and physiotherapy, but the efficacies are limited. An alternative noninvasive treatment low-level laser therapy (LLLT) applied to acupoints is still contradictory and the efficacy needs to be assessed. Methods and Materials We conduct the randomized double-blind control study to investigate the efficacy of a dual-frequency LLLT (combines red light (780?nm) and near-infrared light (830?nm)) in patients suffering knee OA. Participates were randomly assigned into active laser therapy (ALT) and placebo laser therapy (PLT) groups. Subjects in the ALT group were separately treated by laser apparatus at the three acupoints (SP9, SP10, and EX-LE2) on their knee joints under continuous radiation for 15?min at the maximum intensity, three times per week for four weeks. The PLT group used laser apparatus of the same model according to similar procedures without laser light emission. Outcome Measurements including visual analog scale (VAS), pain pressure threshold (PPT), and Lequesne index were used. Results A total of 30 subjects with two-sided knee OA in both groups completed the experiment. Statistically significant decreases were observed in the Lequesne index (5.27?±?3.26 vs. 10.83?±?3.83), conscious VAS 4 weeks after treatment (moving: 2.87?±?1.13 vs. 5.67?±?1.72; resting: 0.33?±?0.62 vs. 2.67?±?1.29), and the increase was noted in PPT (21.23?±?1.82?kg vs. 13.02?±?1.46?kg) in the ALT group compared with the PLT group. Conclusion It appears that the knee OA pain and disability can be decreased after a dual-frequency LLLT applied to acupoints (SP9, SP10, and EX-LE2). The clinical efficacy of LLLT is highly related to the therapeutic settings of the laser apparatus; hence, more clinical trials with diffident parameter settings are needed to be further clarified.

Dataset Information

Cartilage-targeting peptide-modified dual-drug delivery nanoplatform with NIR laser response for osteoarthritis therapy.

Publications

Cartilage-targeting peptide-modified dual-drug delivery nanoplatform with NIR laser response for osteoarthritis therapy.

Similar Datasets

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