Nerve Growth Factor-Targeted Molecular Theranostics Based on Molybdenum Disulfide Nanosheet-Coated Gold Nanorods (MoS₂-AuNR) for Osteoarthritis Pain

Abstract

Osteoarthritis (OA) is a leading cause of chronic pain in the elderly worldwide. Yet current diagnosis and therapy for OA pain are subjective and nonspecific with significant adverse effects. Here, we introduced a theranostic nanoprobe based on molybdenum disulfide nanosheet-coated gold nanorods (MoS2-AuNR) targeting never growth factor (NGF), a key player in pain sensation, for photoacoustic pain imaging and near-infrared (NIR) imaging-guided photothermal analgesic therapy. MoS2 coating significantly improved the photoacoustic and photothermal performance of AuNR. Functionalization of MoS2-AuNR nanoprobes by conjugating with NGF antibody enabled active targeting on painful OA knees in a surgical OA murine model. We observed that our functional nanoprobes accumulated in the OA knee rather than the contralateral intact one, and the amount was correlated with the severity of mechanical allodynia in our mouse model. Under imaging guidance, NIR-excited photothermal therapy could mitigate mechanical allodynia and walking imbalance behavior for both subacute and chronic stages of OA in a preclinical setting. This molecular theranostic approach enabled us to specifically localize the source of OA pain and efficiently block peripheral pain transmission.

Molybdenum‐Based Nanomaterials for Photothermal Cancer Therapy

“…Recently, Au et al designed a nerve growth factor‐targeting PA imaging molecular theragnostic nanoprobe based on 2D MoS 2 nanosheet‐coated gold nanorods (MoS 2 ‐AuNR) for osteoarthritis pain imaging and enhanced PTT. [ 206 ] The MoS 2 ‐AuNR nanocomposite can visualize and quantify osteoarthritis pain by the relative intensity of PA signal and effective alleviate pain by PTT.…”

Looking deep inside tissue with photoacoustic molecular probes: a review

“…Another interesting nanoprobe was designed for PA pain imaging and NIR imaging-guided PTT. 171 Osteoarthritis (OA) is one of the most common reasons for painful conditions in the elderly, and precise localization and imaging of pain generators is in great demand. In this work, an anti-NGF- -AuNPs nanocomplex was synthesized via electrostatic interaction between AuNRs and small and then covalent interaction between anti-NGF antibody and -AuNRs.…”

“…PAI-guided PTT has previously been proposed for the imaging and alleviation of pain 171 as well as imaging and ablation of tumors. 106 , 202 – 204 , 227 , 260 , 290 For example, ICG-loaded polydopamine-iron ions coordination nanoparticles (PDA-FE3+-ICG NPs) were reported as PA and MR dual-modal agents, which passively accumulate in the tumor via an EPR effect.…”

Recent advances in pain management based on nanoparticle technologies

“…Conjugation of NGF antibody with molybdenum disulfide nanosheet-coated gold nanorods (MoS2-AuNR) nanoprobes has been shown to active targeting of NGF on painful knees in an osteoarthritis surgical murine model (Fig. 7 ) [ 172 ]. Wherein, addition of MoS2 coating significantly improved the photoacoustic and photothermal performance of AuNR.…”