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Additional file 1: Text S1. Calculation of the photothermal conversion efficiency. Table S1. Name and the molecular weight of the used linker molecules and nomenclatures of the PHNs synthesized with the linker molecules. Fig S1. Optimization of photoinitiator concentration for obtaining homogenous size distribution of GNPs. Fig S2. Hydrodynamic diameter distribution of the M-PHNs according to the reaction time between 1 and 15 min. Fig S3. Hydrodynamic diameters of PNIPAM nanogels without GNPs according to the reaction time. Fig S4. Absorbance spectra of colloidal GNPs and M-PHNs. Insets display the colors of the colloidal solutions. Fig S5. Monitoring of the thermal stability of M-PHNs and PHNs during 10 cycles of the heating/cooling procedure. Fig S6. Narrow scans of the XPS spectra focused on the selected elements of C, N, O, and Au. Fig S7. TEM images of the PHNs with different linker molecules (i.e., MBA (M-PHN), tryptophan (T-PHN), sucrose (S-PHN), PEG-da (P-PHN), alginate (A-PHN), and gelatin (G-PHN)). Fig S8. Optical properties and colloidal stabilities of the PHNs synthesized with different linker molecules. Fig S9. Molecular weights of alginate, PNIPAM, PNIPAM-alg, and A-PHN measured by SLS analysis. Fig S10. Solubility tests using the lyophilized A-PHN with various concentrations in water. Fig S11. Confirmation of the alginate incorporation in the A-PHN via calcium ion-mediated gelation method by adding 100 mM CaCl2. Fig S12. Energy-dispersive X-ray spectroscopy of A-PHN from Fig. 2g. Fig S13. Schematic image of the GNP structures used in the computation at different diameters of PHN. Fig S14. Linear relationship of -ln(θ) versus time obtained from the cooling period of the thermal curve in Fig. 3g. Fig S15. Light-responsive heat generation of dehydrated PHNs under light illumination. Fig S16. Monitoring of the solution temperature under a commercial LED. Fig S17. In situ Raman spectra of A-PHN gels under 785 nm laser illumination. Fig S18. Temperature-dependent 1H-NMR study of A-PHN dispersed in D2O. Fig S19. Standard curve of doxorubicin by absorbance at 480 nm. Fig S20. Drug release kinetics by different power densities of the LED. Fig S21. Monitoring the mean diameters of A-PHN by changing the buffer pH conditions. Fig S22. Monitoring the Raman spectra of released dox under temporally controlled light modulation. Fig S23. Colloidal stability of A-PHNs under different biological media. Fig S24. Biocompatibility tests using MTT assay to A375P. Fig S25. Images of Pearson’s colocalization coefficient (k) plots for dox versus Hoechst from Fig. 5e (i). Fig S26. Cellular internalization of A-PHNs into A375P cell. Fig S27. Computational simulation results of heat generation from vesicles including A-PHN. Fig S28. Observation of the damage to the cytoskeleton by A-PHNs under exposure to 532 nm laser at 3.5 W/cm2. Fig S29. Confocal fluorescent images of endocytic vesicles before and after laser illumination. Fig S30. Observation of nuclear fragments in A375P cells after treatment with ptx, A-PHN, and ptx@A-PHN (with light exposure), respectively.

Developing cellular therapies is not straightforward. This Perspective summarizes the experience of a group of academic stem cell investigators working in different clinical areas and aims to share insight into what we wished we knew before starting. These include (1) choosing the stem cell line and assessing the genome of both the starting and final product, (2) familiarity with GMP manufacturing, reagent validation, and supply chain management, (3) product delivery issues and the additional regulatory challenges, (4) the relationship between clinical trial design and preclinical studies, and (5) the market approval requirements, pathways, and partnerships needed.

Additional file 1: Figure S1. Simulation of scattering spectra according to the number of graphene layers on SNP. (a) 110 nm SNP. (b) 120 nm SNP. (i) Full spectrum. (ii-iv) Plots showing shifts of λmax (ii), FWHM (iii), and scattering cross-section (σsc) (iv). Figure S2. Simulation of scattering spectra according to the number of graphene layers on GNP. (a) 55 nm GNP. (b) 60 nm GNP. (i) Full spectrum. (ii–iv) Plots showing shifts of λmax (ii), FWHM (iii), and scattering cross-section (σsc) (iv). Figure S3. Representative TEM images of the used SNPs. The average size (for n = 40) was observed to be 101.6 ± 5.0 nm (mean ± SD, nm). Scale bars represent 25 nm. Figure S4. TEM images of the used GNPs. Average size (for n = 40) was 49.5 ± 2.6 nm. Scale bars represent 25 nm. Figure S5. Scattering properties of the plasmonic GNP-graphene interface. (a) Dark-field scattering images of the graphene covered-plasmonic GNP with increasing number of graphene layers. The scale bars represent 10 µm. (b) Corresponding scattering spectra measured for the GNPs with increasing number of graphene layers. (c) Plots for the shifts in terms of λmax (i), FWHM (ii), and intensity (iii) with increasing the graphene layer on the GNP. Figure S6. Changes in photoluminescence (PL) intensities of graphene-covered NPs. (a) SNP. (b) GNP. (i) Schematic diagram, (ii) PL spectrum, and (iii) Plot for the change in PL intensity of NP at 550 nm in the presence of graphene layer. Figure S7. Fluorescence images of intracellular ROS in cells. (a) HDF, (b) NaAsO2-exposed HDF, and (c) A375P. The green fluorescence indicates intracellular ROS visualized by staining with a ROS indicating dye, 2,7-dichlorofluoroscein diacetate (DCFDA). The scale bars represent 50 µm.