The penetration of nanomedicine into solid tumor still constitutes a great challenge for cancer therapy, which lead to the failure of thorough clearance of tumor cells. Aiming at solving this issue, lots of encouraging progress has been made in the development of multistage nanoparticles triggered by various stimuli in the past few years. Besides, the therapeutical effects of nanoagents are also greatly impacted by the complex tumor microenvironment, and remodeling tumor microenvironment has become another important approach for promoting nanoparticles penetration. In this review, we summarize and analyze recent research progress and challenges in promoting nanoparticle penetration based on two kinds of different strategies, which include size shrinkable nanoparticles and priming tumor microenvironments. Especially, many recent reported multi-strategy approaches based on particle size reduction in conjugated with other therapeutic strategies are discussed. And we expect to provide some useful enlightenments and proposals on nanotechnology-based drug delivery systems for more effective therapy of solid tumors.

纳米药物向实体瘤的渗透仍然构成癌症治疗的巨大挑战，这导致无法彻底清除肿瘤细胞。为了解决该问题，在过去几年中，在各种刺激下触发的多级纳米颗粒的开发方面已经取得了令人鼓舞的进展。此外，复杂的肿瘤微环境也极大地影响了纳米剂的治疗效果，重塑肿瘤微环境已成为促进纳米颗粒渗透的另一重要途径。在这篇综述中，我们总结和分析了基于两种不同策略（包括尺寸可收缩的纳米粒子和引发肿瘤微环境）在促进纳米粒子渗透方面的最新研究进展和挑战。尤其，讨论了许多最近报道的基于粒度减小并结合其他治疗策略的多策略方法。我们希望对基于纳米技术的药物递送系统提供更有益的启示和建议，以更有效地治疗实体瘤。