Response to stimuli is a prevalent phenomenon in life. Artificial functional intelligent materials are designed to recognize a specific stimulus and respond with a predetermined output, returning to the original state in the absence of the stimulus. One very promising application of stimuli-responsive materials is the controlled delivery of substances at the nanoscale. The response of these materials to a given stimulus can provide the mechanical and chemical changes that modulate the release of the cargo from the nanocarrier. Such control allows the development of systems that can be optically traced and deliver bioactive payload at a specific location, in the desired amount and in a timely manner. Hybrid nanocarriers with a mesoporous silica nanoparticle (MSN) core and a polymer shell offer numerous design advantages: they can be obtained by a fully controllable low-temperature purely aqueous sol-gel method; feature well-defined particle morphology and diameter (15 nm to >100 nm) with tunable pore size (2–8 nm) and pore geometry (ordered or worm-like); allow versatile independent inner and outer functionalization; and have large cargo capacity (pore volume >1 ml/g).[1-3] Covalent grafting of stimuli-responsive polymers to the MSN outer surface can be used to obtain on-demand cargo release by controlling the diffusion of the cargo from the MSN pores. [4,5] Furthermore, the inner pore surface can also be modified to control the interaction with the cargo, for example, to improve the efficiency of ON:OFF release control, [5] or to frustrate crystallization of the cargo. [6] Smart hybrid silica nanocarriers offer excellent performance and versatility for different biomedical applications. 

Acknowledgments: FCT project PTDC/CTM-COM/1581/2021 (DOI: 10.54499/PTDC/CTM-COM/1581/2021). CQE is a Research Unit funded by FCT through UIDB/00100/2020 (DOI: 10.54499/UIDB/00100/2020) and UIDP/00100/2020 (DOI: 10.54499/UIDP/00100/2020); IMS is an Associate Laboratory funded by FCT through LA/P/0056/2020 (DOI: 10.54499/LA/P/0056/2020). 

References:
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[3] Tavares, M.T.; Oliveira, M.B.; Gaspar, V.M.; Mano, J.F.; Farinha, J.P.S.; Baleizão, C., Advanced Biosystems 2020, 12, 2175. 
[4] Ribeiro, T.; Coutinho, E.; Rodrigues, A.S.; Baleizão, C.; Farinha, J.P.S., Nanoscale 2017, 36, 13485 
[5] Gonçalves, J.; Lopes, A.; Baleizão, C.; Farinha, J.P.S., Pharmaceutics 2021, 13, 716 
[6] Figari, G.; Gonçalves, J.; Diogo, H.P.; Dionísio, M.; Farinha, J.P.S.; Viciosa, M.T., Pharmaceutics 2023, 15, 1624 .