Biodegradable Polymeric Assemblies for Biomedical Materials - Polymers in Nanomedicine - page 91

a

+

Control

Heparin PEI

HPEI

O

H
N

EDC / NHS

R C OH + R ′ NH 2

R C R ′

EP / HPEI

VSVMP / HPEI

b c

0.6 200

160

0.4

120

80

0.2

40

Heparin-PEI nano-gel

0 0

Control HPEI EP / HPEI VSVMP / HPEI Control HPEI EP / HPEI VSVMP / HPEI

Fig. 15 Left : Heparin-PEI nanogel. Right : Effect of treatment with heparin-PEI nanogel ( HPEI ),
pEP-loaded nanogel ( EP/HPEI ), and pVSVMP-loaded nanogel ( VSVMP/HPEI ). (a) Photograph
of lungs bearing metastases of C-26 colon carcinomas in each treatment group. (b) Weight of lungs
bearing pulmonary metastases of C-26 colon carcinoma in each treatment group. (c) Number of
pulmonary metastatic nodules in each treatment group. Reprinted from [ 259 ] with permission

Wei et al. prepared heparin-polyethyleneimine (HPEI) nanogel, which was
designed for pVSVMP (plasmid expressing vesicular stomatitis virus matrix protein)
delivery to treat C-26 colon carcinoma in vitro and in vivo (Fig. 15 ). The HPEI
nanogel is a novel nonviral gene vector, and able to efficiently transfect pVSVMP
into C-26 colon carcinoma cells in vitro, inhibiting cell proliferation through apopto-
sis induction. Application of pVSVMP/HPEI complexes can efficiently inhibit the
growth of colon carcinoma in vivo. A new and interesting genetic cancer therapy
protocol for treatment of colon cancer using the HPEI nanogel was proposed [ 259 ].
Na et al. reported a HA-bearing photosensitizer moiety as a new type of photody-
namic therapy agent [ 260 ]. After incubation of the HA/photosensitizer conjugate
nanogels with cells, the degradation of the HA by enzymes in endosomes and
lysosomes was monitored as a dissipation of the autoquenching behavior (Fig. 16 ).
The nanogels also exhibited HA-induced tumor-homing properties, resulting in a
rapid internalization rate. Moreover, the nanogels indicated high cytotoxicity against
cancer cells under light emission, which was comparable with the free photosensi-
tizer, but very low cytotoxicity without light.
We have reported biodegradable polysaccharide- g -PLA nanogels. PLA was
chosen as physically crosslinking segments based on its hydrophobicity and biode-
gradability. Relatively short PLLA (oligolactide, OLLA) chains were introduced to
pullulan or Dex by a coupling reaction [ 162 - 164 ]. We prepared protein-loaded
Dex- g -OLLA nanogels using lysozyme as model protein and found that

the