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Initially, the IOMN nanoparticles were synthesized using a modified pyrolysis-based method in
organic solvent. These hydrophobic core IOMN nanoparticles were converted into the biocompatible
water soluble form with the use of amphiphilic polymer that interacted with the original hydrophobic
oleate coating resulting in a double layered structure with carboxyl groups on the surface.
One of the major advantages for IOMN with PEG (IOMN -LA-PEG) as a drug carrier is that the
degradation of Dox could be effectively reduced by conjugating Dox on the surface of IOMN -LA-
PEG. The degree of freedom of Dox IOMN -LA-PEG was limited to prevent its molecular distortion
and hence increase its half-life. In addition, IO-LP-PEG- could cause DNA crosslink more serious,
resulting in a lower DNA expression and a higher CRC cells. apoptosis. Finally, the accumulation of
IOMN -LA-PEG in cancer tumors could be enhanced by applying a magnetic field in the tumor to
increase the degree of DNA crosslink and to reduce the damage of normal organs. (citation)
o Formation of LA-PEG-PD-L1
PD-L1 is a type I transmembrane protein that was recently implicated in the etiology of CRC and
shown to be a biomarker of CRC. (Luan, et al., 2016) Furthermore, PD-L1overexpression is known
to be significantly associated with prognosis and overall survival in curatively resected CRC
patients, (Morihiro, et al., 2017) and anti-PD-L1 antibody ie used her for target delivery to CRC.
LA-PEG-PD-L1 was conjugated by reacting the ε-amino groups on the lysine residue of the
anti-PD-L1 antibody with the α-terminal end group LA-PEG-NHS (Zhou, Zhang, Zhang, Ma,
& Su, 2016) through amide linkage. (Fakhrossadat Emami, 2019)
o Formation of LA-PEG-DOX
o LA-PEG-DOX is conjugated by reaction the amine group of DOX with the α-terminal end group the
LA-PEG-NHS (Zhou, Zhang, Zhang, Ma, & Su, 2016) through (−CO-NHR) amide linkage.
(Fakhrossadat Emami, 2019)
o Formation of DOX-LA-PEG-PD-L1
la-polyethylene glycol modification of MNP improve the circulation time of therapeutic agents or
delivery devices. The hydrophilic PEG can improve the biocompatibility of the delivery system
because most of the biological environment is hydrophilic, and biocompatibility appears to be
correlated with the degree of hydrophilicity exhibiting on the surface. (Po-Chin Liang, 2016) (Li,
Takashima, Yuba, Harada, & Kono, 2014).
a. Therapeutic action
i. Cytotoxicity
ii. mechanism
b. pros and cons
i. prose
ii. cons
4. reference
5.
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Byrne, J. D., Betancourt, T., & Brannon-Peppas, L. (2008). Active Targeting Schemes for Nanoparticle
Systems in Cancer Therapeutics. Adv. Drug Delivery Rev. 2008, 60 (15), 1615−1626, 1615-1626.
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1 expression predicts survival in patients with gastric carcinoma with microsatellite instability.
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combination elicits antitumor immunity against advanced metastatic cancer. Nature
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Po-Chin Liang, C.-F. C.-R.-Y.-Y.-L. (2016). Doxorubicin-modified magnetic nanoparticles as a drug delivery
system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy.
International Journal of Nanomedicine.
Rebecca L. Siegel, K. D. (2020). Cancer Statistics, 2020. CA CANCER J CLIN, VOLUME 70. Retrieved from
https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21590
Rezazadeh, M., Akbari, V., Amuaghae, E., & Emami, J. (2018). Preparation and characterization of an
injectable thermosensitive hydrogel for simultaneous delivery of paclitaxel and doxorubicin. Res.
Pharm. Sci, 181.
Sin-Tzu Ning, S.-Y. L. (2016). Targeting Colorectal Cancer Stem-Like Cells with Anti-CD133. ACS Appl.
Mater. Interfaces, 17793-17804.
Tazi, I., Nafil, H., & Mahmal, L. (2012). Monoclonal Antibodies in Hematological Malignancies: Past.
Present and Future. J. Cancer Res, 281-269.
Zhao, L., Zhu, J., Cheng, Y., Xiong, Z., Tang, Y., Guo, L., . . . Zhao, J. (2015). Chlorotoxin-conjugated
multifunctional dendrimers labeled with radionuclide 131I for single photon emission computed
tomography imaging and radiotherapy of gliomas. ACS Appl. Ma, 19798-19808.
Zheng, M., Yue, C., Ma, Y., Gong, P., Zhao, P., Zheng, C., . . . Cai, L. (2013). . Single-step assembly of DOX/
ICG loaded lipid−polymer nanoparticles for highly effective chemophotothermal combination
therapy. ACS Nano 2013, 2056.
Zhou, Z., Zhang, J., Zhang, Y., Ma, G., & Su, Z. (2016). speceific Conjugation of the Hinge Region for
Homogeneous Preparation of Antibody Fragment-Drug Conjugate: A Case Study for Doxorubicin-
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References
Anders, C. K., Adamo, B., Karginova, O., Deal, A. M., Rawal, S., Darr, D., . . . Zamboni, W. C. (2013).
Pharmacokinetics and Efficacy of PEGylated Liposomal Doxorubicin in an intracranial Model of
brest cancr. PLoS ONE, 61369.
Byrne, J. D., Betancourt, T., & Brannon-Peppas, L. (2008). Active Targeting Schemes for Nanoparticle
Systems in Cancer Therapeutics. Adv. Drug Delivery Rev. 2008, 60 (15), 1615−1626, 1615-1626.
Cho, J., Lee, J., Bang, H., Kim, S. T., Park, S. H., An, J. Y., . . . Kim, k. (2017). Programmed cell death-ligand
1 expression predicts survival in patients with gastric carcinoma with microsatellite instability.
Oncotarget.
Correale, P., Cusi, M. G., Del Vecchio, M. T., Tsang, K. Y., Marsili, S., Placa, M. L., . . . all, e. (2005). Chemo-
immunotherapy of metastatic colorectal carcinoma with gemcitabine plus FOLFOX 4 followed by
subcutaneous granulocyte macrophage colony-stimulating factor and interleukin-2 induces
strong immunologic and antitumor activity in metastatic colon cance. J. Clin. Oncol., 8950-8958.
Correale, P., Cusi, M. G., Tsang, K. Y., Del Vecchio, M. T., Marsili, S., Placa, M. L., . . . al, e. (2005). .
Chemo-immunotherapy of metastatic colorectal carcinoma with gemcitabine plus FOLFOX 4
followed by subcutaneo factor and interleukin-2strong immunologic and antitumer activity in
metatastatic colon cancer patients. J. Clin. Oncol, 8950-8958.
Cronin, K. A., Lake, A. J., Scott, S., Sherman, R. L., Noone, A., Howlader, N., . . . Ma, J. ( 2018). Annual
Report to the Nation on the Status of Cancer part I. National cancer statistics. Cancer.
Evans, J. P., Sutton, P. A., Winiarski, B. K., Fenwick, S. W., Vimalachandran, D., Tweedle, E. M., . . .
Kitteringham, N. R. (2016). From mice to men Murine models of colorectal cancer for use in
translational research. Crit. Rev. Oncol./Hematol, 98 , 94−105.
Greish, K. (2010). . Enhanced Permeability and Retention (EPR) Effect for Anticancer Nanomedicine Drug
Targeting. Methods Mol. Biol, 25−37.
Lammers, T., Hennink, W. E., & Storm, G. (2008). Tumour-Targeted Nanomedicines: Principles and
Practice. Br. J. Cancer, 392-397.
Mahon, E., Salvati, A., Baldelli Bombelli, F., Lynch, I., & Dawson, K. A. (2012). Designing the Nanoparticle-
Biomolecule Interface For “targeting and Therapeutic Delivery. J. Controlled Release, 164-174.
Manchun, S., Dass, C. R., Cheewatanakornkool, K., & Sriamornsak, P. (2015). Enhanced anti-tumor effect
of pH-responsive dextrinnanogels delivering doxorubicin on colorectal cancer. Carbohydr.
Polym., 126, 222−230.
Nam, J., Son, S., Ochyl, L. J., Kuai, R., & Schwendeman, A. M. (2018). . Chemo-photothermal therapy
combination elicits antitumor immunity against advanced metastatic cancer. Nature
communacation.
Po-Chin Liang, C.-F. C.-R.-Y.-Y.-L. (2016). Doxorubicin-modified magnetic nanoparticles as a drug delivery
system for magnetic resonance imaging-monitoring magnet-enhancing tumor chemotherapy.
International Journal of Nanomedicine.
Rebecca L. Siegel, K. D. (2020). Cancer Statistics, 2020. CA CANCER J CLIN, VOLUME 70. Retrieved from
https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21590
Rezazadeh, M., Akbari, V., Amuaghae, E., & Emami, J. (2018). Preparation and characterization of an
injectable thermosensitive hydrogel for simultaneous delivery of paclitaxel and doxorubicin. Res.
Pharm. Sci, 181.
Sin-Tzu Ning, S.-Y. L. (2016). Targeting Colorectal Cancer Stem-Like Cells with Anti-CD133. ACS Appl.
Mater. Interfaces, 17793-17804.
Tazi, I., Nafil, H., & Mahmal, L. (2012). Monoclonal Antibodies in Hematological Malignancies: Past.
Present and Future. J. Cancer Res, 281-269.
Zhao, L., Zhu, J., Cheng, Y., Xiong, Z., Tang, Y., Guo, L., . . . Zhao, J. (2015). Chlorotoxin-conjugated
multifunctional dendrimers labeled with radionuclide 131I for single photon emission computed
tomography imaging and radiotherapy of gliomas. ACS Appl. Ma, 19798-19808.
Zheng, M., Yue, C., Ma, Y., Gong, P., Zhao, P., Zheng, C., . . . Cai, L. (2013). . Single-step assembly of DOX/
ICG loaded lipid−polymer nanoparticles for highly effective chemophotothermal combination
therapy. ACS Nano 2013, 2056.
Refrence
(9) Rezazadeh, M.; Akbari, V.; Amuaghae, E.; Emami, J. Preparation and characterization of an injectable
thermosensitive hydrogel for simultaneous delivery of paclitaxel and doxorubicin. Res. Pharm. Sci. 2018, 13 (3),
181.
(6) Manchun, S.; Dass, C. R.; Cheewatanakornkool, K.; Sriamornsak, P. Enhanced anti-tumor effect of pH-responsive
dextrin nanogels delivering doxorubicin on colorectal cancer. Carbohydr. Polym. 2015, 126, 222−230 (smorkamol
manchun, 2015)
(12) Correale, P.; Cusi, M. G.; Tsang, K. Y.; Del Vecchio, M. T.; Marsili, S.; Placa, M. L.; Intrivici, C.; Aquino,
A.; Micheli, L.; Nencini,C.; et al. Chemo-immunotherapy of metastatic colorectal carcinoma with gemcitabine plus
FOLFOX 4 followed by subcutaneous granulocyte macrophage colony-stimulating factor and interleukin-2 induces strong
immunologic and antitumor activity in metastatic colon cancer patients. J. Clin. Oncol. 2005, 23 (35), 8950−8958. (Correale,
et al., 2005)
(17) (17 (Nam, Son, Ochyl, Kuai, & Schwendeman, 2018).
12…….Zhao, L.; Zhu, J.; Cheng, Y.; Xiong, Z.; Tang, Y.; Guo, L.; Shi, X.; Zhao, J. Chlorotoxin-conjugated multifunctional
dendrimers labeled with radionuclide 131I for single photon emission computed tomography imaging and radiotherapy of
gliomas. ACS Appl. Mater. Interfaces 2015, 7 (35), 19798−19808 (Zhao, et al., 2015)
18… (18) Zheng, M.; Yue, C.; Ma, Y.; Gong, P.; Zhao, P.; Zheng, C.; Sheng, Z.; Zhang, P.; Wang, Z.; Cai, L. Single-step
assembly of DOX/ ICG loaded lipid−polymer nanoparticles for highly effective chemophotothermal combination therapy. ACS
Nano 2013, 7 (3), 2056− 2067. (Zheng, et al., 2013)
(1) Anders, C. K.; Adamo, B.; Karginova, O.; Deal, A. M.; Rawal, S.; Darr, D.; Schorzman, A.; Santos, C.; Bash, R.; Kafri, T.;
Carey, L.; Miller, C. R.; Perou, C. M.; Sharpless, N.; Zamboni, W. C. Pharmacokinetics and Efficacy of PEGylated Liposomal
Doxorubicin in an Intracranial Model of Breast Cancer. PLoS One 2013, 8 (5), e61359. (Anders, et al., 2013)
(4 (Greish, 2010)