The synergistic effects of kPa-scale elastic modulus and size of poly(N-isopropylacrylamide)/sodium alginate nanospheres on endocytosis.

To improve the endocytosis efficiency of nanomaterials by cells, we synthesized poly(N-isopropylacrylamide)/sodium alginate nanospheres with tunable elastic moduli (30 and 300 kPa) and sizes (45 nm, 105 nm, and 220 nm). Cell endocytosis experiments demonstrated that particle size is the primary factor governing endocytosis efficiency, whereas modulus plays a regulatory role in specific endocytic routes. Also, the more the endocytosis pathways are involved, the higher the endocytosis efficiency is. As the synergistic effects of elastic moduli and size, the small and stiff nanosphere (45 nm and 300 kPa) exhibited the most efficient cellular endocytosis. When loaded with doxorubicin (DOX), this nanosphere achieved much improved anticancer effects, reducing cell viability to one-third of free DOX. This study may provide information for the design of nano drug carriers with kPa modulus.