**4. Conclusions**

Poly(glycerol sebacate) was, for the first time, exploited for the encapsulation of curcumin, with the aim to design a nanosized anticancer system characterized by high stability even under physiological conditions and strong biological activity through an easy, scalable and reproducible technique. Different experimental conditions have been tested, aimed to define the most promising formulations in terms of particle stability and size. Indeed, the curcumin-loaded sample PGS5.0C0.5 and the respective unloaded formulation PGS5.0Blank, were selected in virtue of their stability even when diluted in simulated cells medium. Stability and morphological analysis were performed through DLS and TEM analysis which allowed confirmation of their nanosized dimension of about 150 nm and spherical shape. Finally, curcumin-loaded PGS-NPs displayed a higher cytotoxic effect compared to free curcumin, thanks to the higher solubility in physiological conditions. Consistent with this, the developed curcumin-loaded PGS-NPs were capable of inducing apoptosis by promoting the expression of *p53*, its target gene, *p21*, involved in cell cycle arrest and the pro-apoptotic *Bax* gene. Finally, a reduction of *HPV E6* expression was observed, suggesting that curcumin-loaded PGS-NPs can exert a significant anti-HPV activity, thus possibly preventing pre-cancer lesions. Overall, our results show that curcumin-loaded PGS-NPs may represent a possible adjuvant therapy for delaying/treating cervical cancer cells.

**Supplementary Materials:** The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/molecules27206997/s1.

**Author Contributions:** Conceptualization, L.V. and K.P.; investigation, A.M. (Alessio Massironi), D.M., A.M. (Alessandra Marinelli), M.T., S.G.; writing—original draft preparation, A.M. (Alessio Massironi), A.M. (Alessandra Marinelli), M.T., S.G.; writing—review and editing, S.M., K.P., L.V., M.A.O.; supervision, L.V, S.M., K.P., M.A.O.; funding acquisition: K.P., D.M., L.V., S.M., M.A.O. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research was partially funded by the Università degli Studi di Milano (Linea 3—Piano di Sostegno alla Ricerca 2020 Seal of Excellence project "To-PoST" grant RV\_PSR\_SOE\_2020\_GDICA to L.V, S.M, M.A.O.; the Linea 2—Piano di Sostegno alla Ricerca 2020 Seal of Excellence grant PSR2020\_DIP\_005\_PI\_ACOLO to D.M.), and by the Fondazione Umberto Veronesi (Grant 2014 to K.P.; Grant Fellowship to A.M2).

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** The authors thank Nadia Santo for TEM analyses.

**Conflicts of Interest:** The authors declare no conflict of interest.

**Sample Availability:** Samples of the compounds are not available from the authors.
