Wen Amy M, Lee Karin L, Cao Pengfei, Pangilinan Katrina, Carpenter Bradley L, Lam Patricia, Veliz Frank A, Ghiladi Reza A, Advincula Rigoberto C, Steinmetz Nicole F
Department of Chemistry, North Carolina State University , Raleigh, North Carolina 27695, United States.
Bioconjug Chem. 2016 May 18;27(5):1227-35. doi: 10.1021/acs.bioconjchem.6b00075. Epub 2016 Apr 27.
Photodynamic therapy (PDT) is a promising avenue for greater treatment efficacy of highly resistant and aggressive melanoma. Through photosensitizer attachment to nanoparticles, specificity of delivery can be conferred to further reduce potential side effects. While the main focus of PDT is the destruction of cancer cells, additional targeting of tumor-associated macrophages also present in the tumor microenvironment could further enhance treatment by eliminating their role in processes such as invasion, metastasis, and immunosuppression. In this study, we investigated PDT of macrophages and tumor cells through delivery using the natural noninfectious nanoparticle cowpea mosaic virus (CPMV), which has been shown to have specificity for the immunosuppressive subpopulation of macrophages and also targets cancer cells. We further explored conjugation of CPMV/dendron hybrids in order to improve the drug loading capacity of the nanocarrier. Overall, we demonstrated effective elimination of both macrophage and tumor cells at low micromolar concentrations of the photosensitizer when delivered with the CPMV bioconjugate, thereby potentially improving melanoma treatment.
光动力疗法(PDT)是提高对高度耐药且侵袭性黑色素瘤治疗效果的一条有前景的途径。通过将光敏剂附着于纳米颗粒,可以赋予递送的特异性,以进一步减少潜在的副作用。虽然PDT的主要重点是破坏癌细胞,但对肿瘤微环境中也存在的肿瘤相关巨噬细胞进行额外靶向,可通过消除它们在侵袭、转移和免疫抑制等过程中的作用来进一步增强治疗效果。在本研究中,我们通过使用天然非感染性纳米颗粒豇豆花叶病毒(CPMV)进行递送,研究了对巨噬细胞和肿瘤细胞的光动力疗法,CPMV已被证明对巨噬细胞的免疫抑制亚群具有特异性,并且还靶向癌细胞。我们进一步探索了CPMV/树枝状聚合物杂化物的缀合,以提高纳米载体的药物负载能力。总体而言,我们证明了当与CPMV生物共轭物一起递送时,在低微摩尔浓度的光敏剂下可有效消除巨噬细胞和肿瘤细胞,从而有可能改善黑色素瘤的治疗。