Understanding the correlation between the molecular structure and physicochemical properties of the colloidal particles and their intracellular uptake and response is one of the most paramount perquisites for their biomedical applications. Previously we have gained fruitful results and experiences on ordinary particle design and preparation, and interactions between colloidal particles and cells, while our collaborative partner possess the strong ability in preparation, targeted delivery and in vivo tracking of responsive polymer colloidal particles. Aiming at the insight study of interaction between themore advancingresponsive colloidal particles and in vitro cells and in vivo tissues, novel polymeric particles with tunable chemical structure and responsiveness to external stimuli such as temperature, pH, ionic strength and biomolecular concentration shall be designed and fabricated. The in vitro cellular uptake and intracellular response process of the particles shall be clarified in terms of the cellular uptake rate, amount, pathways and intracellular distribution. Studies also cover the responsiveness of the particles inside the cells, such as the variation of chemical composition, molecular structures and physical properties. The alteration of cell viability, specific functions, phenotype and genetic toxicity as a result of the internalization of particles shall be studied too. Based on these results, cellular uptake and transportation principles shall be summarized and models shall be suggested. Finally, the influence of responsive colloidal particles on the in vivo tissue accumulation and alteration shall be studied in animal models.