# Biodegradable Polymeric Architectures via Reversible Deactivation Radical Polymerizations
## 2 Biodegradable Polymeric Architectures
### Hydrogels and Nanogels
#### 2.3.2 Nanogels  
Nanogels have drawn enormous attention due to their applications as targeted drug delivery scaffolds in biomedical science. [PERSON]'s group is pioneering the fabrication of hyperbranched polymeric architectures, particles, hydrogels and nanogels using ATRP strategies [85]. They reported the synthesis of stable biodegradable nanogels cross-linked with disulfide linkages using inverse miniemulsion ATRP methods. The biodegradation in the presence of glutathione tripeptide can trigger the release of encapsulated molecules including rhodamine 6 G, a fluorescent dye and doxorubicin (Dox), an anticancer drug, as well as facilitate the removal of empty vehicles [86]. They also prepared biodegradable nanogels as delivery carriers for carbohydrate drugs using ATRP in a cyclohexane inverse miniemulsion in the presence of a disulfide functionalized dimethacrylate cross-linker. These nanogels exhibited the high loading efficiency of rhodamine B isothiamate-dextran (RITC-Dx) exceeding 80% [87]. The same inverse miniemulsion ATRP strategy was also utilized to make biodegradable nanogels. Likewise, nanogels that can be degraded under various pH conditions were also prepared from biodegradable amphiphilic polymers synthesized by ATRP combined with ROP synthetic methodologies [88]. Recent advances in drug carrier design in the field of photodynamic therapy (PDT) have stimulated the development of numerous sophisticated drug delivery carriers. [PERSON] and coworkers designed a novel biodegradable and biocompatible nanogels used as PDT carriers. The nanogels were synthesized through ATRP method using inverse miniemulsion and their biodegradability was determined in the presence of glutathione. The model photosensitizer (PS) was encapsulated in the biodegradable nanogels by simple mixing and sonication. The cellular uptake and the cytotoxicity of the nanogels before and after laser irradiation were determined. The results showed that the Ce6-loaded  
Figure 7: (**a**) Schematic representation of micelle gelation at 37 \({}^{\circ}\)C and polymer architecture coordinating with STEM-EDS element maps; (**b**) TEM images of PPS60-\(b\)-PDMA150-\(b\)-PNIPAAM150 micelles at 25 and 37 \({}^{\circ}\)C; (**c**) STEM-EDS element maps for sulfur (red) and oxygen (green) of PPS60-\(b\)-PDMA150-\(b\)-PNIPAAM150 core–shell compartments at 37 \({}^{\circ}\)C with image thresholding and background subtraction. Core-forming PPS produces the red signal for sulfur, while oxygen (appearing green) is present in the PDMA and PNIPAAM corona-forming blocks. Copyright 2014, American Chemical Society. nanogels did not influence the cellular viability of the cells before light irradiation. Under light exposure, the Ce6-nanogel complex revealed strong photoactivity. These nanogels may enhance therapeutic efficacy of PSs without any complex chemical modifications with PSs (Figure 8) [89]. The stability of encapsulation in self-assembled system is usually limited by the requisite concentration for self-assembly formation. Once the encapsulation is achieved, the lack of targeting molecules on the drug carriers will compromise the efficiency for targeted delivery. To tackle this issue, [PERSON] and coworkers successfully fabricated surface-functionalized polymer nanogels with facile hydrophobic guest encapsulation capabilities [90]. These biodegradable nanogels were first prepared from pyridyl disulfide pedant random copolymers that were prepared through RAFT mechanism via cross-linking through disulfide bonding, followed by the surface modification with a thiol-modified cell-penetrating peptide, Tat-SH. The internalization of Tat-SH modified nanogels occurred much more readily than that observed with the control gels, confirming the effectiveness of the modification of the nanogel surface. This presents a clear method for incorporating ligands onto the polymer nanoparticles and thus achieves specificity to pathogenic cells.