靶向肿瘤进化的创新纳米药物

Tumor evolution-targeted nanomedicine^(EVT)

近年来,随着纳米技术的发展,将纳米材料应用于肿瘤靶向治疗有望极大地改善肿瘤治疗效果.纳米药物因其可增加药物溶解性、延长血液循环时间、提高靶向性、提升治疗效果并降低毒副作用等特点而备受研究者关注.肿瘤生物学研究表明,肿瘤始终处于动态的进化和演化过程之中,由于其基因组的不稳定性,肿瘤细胞可在肿瘤内部的生存压力下进行自然选择,或在外来治疗压力(放射治疗、化学治疗、分子靶向治疗和免疫治疗)作用下,持续产生基因突变并扩增,从而导致肿瘤增殖、耐药和转移.因此,肿瘤治疗方案理应随着肿瘤的进化过程而变化和调整.然而,现阶段纳米药物的设计对肿瘤进化的临床现实缺乏充分考虑.本文提出靶向肿瘤进化的创新纳米药物的构想,即从肿瘤进化的临床现实出发,尽可能灵敏地、准确地、全面地跟踪肿瘤在自然选择、治疗压力下出现的增殖、耐药、转移等过程,掌握该过程中的进化特征,并基于这些进化特征设计创新纳米药物,能够有策略地、主动地、及时地动态调整纳米药物及给药方案,结合临床上其他多种治疗药物和方法,力争把肿瘤控制为慢性疾病.

With the recent development of nanotechnology,the integration of nanotechnology with cancer therapy significantly improves the patients’treatment outcomes.Nanomedicines have drawn great attention due to their increased drug solubility,prolonged blood circulation,increased accumulation and retention in the tumors,thereby ultimately resulting in improved therapeutic effects and biosafety.Notably,tumor biology study has indicated that tumor is constant in dynamic evolution under the internal survival pressure as well as external treatment pressure during therapeutic interventions,including radiotherapy,chemotherapy,molecular targeted therapy,and immunotherapy.These pressures further induced genetic mutations or amplifications of specific genes,resulting in tumor proliferation,drug resistance,and metastasis.Therefore,the therapeutic drugs and regimens should be tuned according to the tumor evolution characteristics.Unfortunately,current design of nanomedicines fails to take into consideration of tumor evolution.Herein,we propose a unique concept of tumor evolution-targeted nanomedicine(nanomedicine^(EVT))by fully understanding the tumor evolution process related to proliferation,drug resistance,and metastasis under natural selection or therapeutic pressures.On this basis,nanomedicine^(EVT)could be designed,which therefore would actively,tactically,and timely attack the tumors.In this way,tumors are expected to become chronic diseases by combination of nanomedicine EVT and other therapeutic regimens in clinic.