Efficient penetration and retention of therapeutic agents in tumor tissues can be realized through rational design of drug delivery systems. Herein, a polymer-dendron conjugate, POEGMA-b-p(GFLG-Dendron-Ppa) (GFLG-DP), is presented, which allows a cathepsin-B-triggered stealthy-to-sticky structural transformation. The compositions and ratios are optimized through dissipative particle dynamics simulations. GFLG-DP displays tumor-specific transformation and the consequently released dendron-Ppa is found to effectively accumulate on the tumor cell membrane. The interaction between the dendron-Ppa and the tumor cell membrane results in intracellular and intercellular transport via membrane flow, thus achieving efficient deep penetration and prolonged retention of therapeutic agents in the solid tumor tissues. Meanwhile, the interaction of dendron-Ppa with the endoplasmic reticulum disrupts cell homeostasis, making tumor cells more vulnerable and susceptible to photodynamic therapy. This platform represents a versatile approach to augmenting the tumor therapeutic efficacy of a nanomedicine via manipulation of its interactions with tumor membrane systems.