Redox-Sensitive Targeted Doxorubicin-Loaded Chitosan-based Nanoparticles to Treat Breast Cancer
Main Article Content
Keywords
Breast cancer; Chitosan; Doxorubicin; Hyaluronic acid; Redox-sensitive
Abstract
The positive charge of chitosan (Cs) polymer has limited its utilization as a carrier for doxorubicin (DOX). Herein, a Cs derived by covalent linkage to L-Cysteine (L-Cys) was offered to reduce the positive charge of the polymer and to enhance the DOX entrapment efficiency (EE). Hence, the hyaluronic acid-targeted DOX-loaded Cs-Cys nanoparticles (HA/Cs-CysNPs-DOX) were synthesized
as a redox-responsive carrier for intracellular delivery of DOX. At first, the Cs-CysNPs-DOX was synthesized by ion-gelation technique, after which HA was attached by electrostatic interaction as a targeting agent. Ultimately, they were characterized in terms of size, zeta potential, EE, drug loading (DL), and morphology. HA/Cs-CysNPs-DOX based on the novel copolymers displayed an appropriate
EE for DOX and redox-stimuli drug release. The hemolysis assay proved the safety and hemocompatibility of the NPs, which confirms their intravenous application. In vitro drug release indicated high stability in physiological conditions with a glutathione (GSH) dependence drug release. The cytotoxicity and apoptosis of HA/Cs-CysNPs-DOX were also studied by investigating MCF-7 cells with various concentrations and times. A considerable cytotoxicity enhancement was displayed for HA/Cs-CysNPs-DOX compared to Cs-CysNPs-DOX and free DOX, while no cytotoxicity effects were found for free NPs. The caspase-3 activity showed that apoptosis was enhanced by raising the concentration of DOX, and the free NPs did not exhibit any caspase-3 activity. Overall, the developed
HA/Cs-CysNPs-DOX displayed a high potential for targeted therapy and effective applications in biomedical investigation.
References
1. Alqosaibi AI (2022) Nanocarriers for anticancer drugs: Challenges and perspectives. Saudi J Biol Sci. 29:103298.
https://doi.org/10.1016/j.sjbs.2022.103298
2. Wang C, Zhang Z, Chen B, Gu L, Li Y, Yu S (2018) Design and evaluation of galactosylated chitosan/graphene oxide nanoparticles as a drug
delivery system. J Colloid Interface Sci. 516:332- 41. https://doi.org/10.3390/polym14112287
3. Wang S-Y, Hu H-Z, Qing X-C, Zhang Z-C, Shao Z-W (2020) Recent advances of drug delivery nanocarriers in osteosarcoma treatment. J Cancer.11:69-82. https://doi.org/10.7150/jca.36588
4. Bajracharya R, Song JG, Patil BR, Lee SH, Noh H-M, Kim D-H, Kim G-L, Seo S-H, Park J-W, Jeong SH, Lee CH, Han H-K (2022) Functional
ligands for improving anticancer drug therapy: current status and applications to drug delivery systems. Drug Deliv. 29:1959-70.
https://doi.org/10.1080/10717544.2022.2089296
5. Chiesa E, Greco A, Riva F, Dorati R, Conti B, Modena T, Genta I (2022) CD44-Targeted Carriers: The Role of Molecular Weight of
Hyaluronic Acid in the Uptake of Hyaluronic Acid-Based Nanoparticles. Pharmaceuticals. 15:103. https://doi.org/10.3390%2Fph15010103
6. Vodyashkin AA, Kezimana P, Vetcher AA, Stanishevskiy YM (2022) Biopolymeric Nanoparticles–Multifunctional Materials of the
Future. Polymer. 14:2287. https://doi.org/10.3390/polym14112287
7. Jesus S, Marques AP, Duarte A, Soares E, Costa JP, Colaço M, Schmutz M, Som C, Borchard G, Wick P, Borges O (2020) Chitosan
Nanoparticles: Shedding Light on Immunotoxicity and Hemocompatibility. Front Bioeng Biotechnol. 8:100.
https://doi.org/10.3389/fbioe.2020.00100
8. George D, Maheswari PU, Begum KMS (2020) Cysteine conjugated chitosan based green nanohybrid hydrogel embedded with zinc oxide
nanoparticles towards enhanced therapeutic potential of naringenin. React Funct Polym. 148:104480.
http://dx.doi.org/10.1016/j.reactfunctpolym.2020.104480
9. M. Ways TM, Lau WM, Khutoryanskiy VV (2018) Chitosan and Its Derivatives for Application in Mucoadhesive Drug Delivery Systems. Polymer.10:267.https://doi.org/10.3390%2Fpolym10030267
10. Hershberger KK, Gauger AJ, Bronstein LM (2021) Utilizing Stimuli Responsive Linkages to Engineer and Enhance Polymer NanoparticleBased Drug Delivery Platforms. ACS Appl Bio Mater. 4:4720-36. https://doi.org/10.1021/acsabm.1c00351
11. Majumder J, Minko T (2021) Multifunctional and stimuli-responsive nanocarriers for targeted therapeutic delivery. Expert Opin Drug Deliv.
18:205-27.https://doi.org/10.1080/17425247.2021.1828339
12. Murugan B, Sagadevan S, Fatimah I, Oh W-C, Hossain MAM, Johan MR (2021) Smart stimuliresponsive nanocarriers for the cancer therapy –
nanomedicine. Nanotechnol Rev. 10:933-53.https://doi.org/10.1515/ntrev-2021-0067
13. Xiang Z, Liu M, Song J (2021) StimuliResponsive Polymeric Nanosystems for Controlled Drug Delivery. Appl Sci. 11:9541.
https://doi.org/10.3390/app11209541
14. Omrani I, Babanejad N, Shendi HK, Nabid MR (2017) Fully glutathione degradable waterborne polyurethane nanocarriers: Preparation, redoxsensitivity, and triggered intracellular drug release. Mater Sci Eng C. 70:607-16. http://dx.doi.org/10.1016/j.msec.2016.09.036
15. Yap WF, Yunus WMM, Yusof NA, Ibrahim NI, Zainudin AA. Characterization and optical properties of L-cysteine/chitosan biocomposite
thin film. 2014.
16. Butowska K, Woziwodzka A, Borowik A, Piosik J (2021) Polymeric Nanocarriers: A Transformation in Doxorubicin Therapies.
Materials (Basel, Switzerland).
14:https://doi.org/10.3390/ma14092135
17. Wang D, Zhang X, Xu B (2021) PEGylated Doxorubicin Prodrug-Forming ReductionSensitive Micelles With High Drug Loading and
Improved Anticancer Therapy. Front Bioeng Biotechnol. 9:https://doi.org/10.3389/fbioe.2021.781982
18. Tan ML, Choong PF, Dass CR (2009) Doxorubicin delivery systems based on chitosan for cancer therapy. J Pharm Pharmacol. 61:131-
42. https://doi.org/10.1211/jpp.61.02.0001
19. Shakil MS, Mahmud KM, Sayem M, Niloy MS,Halder SK, Hossen MS, Uddin MF, Hasan MA (2021) Using Chitosan or Chitosan Derivatives in
Cancer Therapy. Polysaccharides. 2:795-816.https://doi.org/10.3390/polysaccharides204004820. Mazzotta E, De Benedittis S, Qualtieri A,
Muzzalupo R (2019) Actively targeted and redox responsive delivery of anticancer drug by chitosan nanoparticles. Pharmaceutics. 12:26.
https://doi.org/10.3390%2Fpharmaceutics12010026
21. A. B-S, M.D. H, C.E. K, N. L (2002) Thiolated polymers: Stability of thiol moieties under different storage conditions. Sci Pharm. 70:331-
9. https://doi.org/10.3797/scipharm.aut-02-32
22. Helmi O, Elshishiny F, Mamdouh W (2021) Targeted doxorubicin delivery and release within breast cancer environment using PEGylated
chitosan nanoparticles labeled with monoclonal antibodies. Int J Biol Macromol. 184:325-38. https://doi.org/10.1016/j.ijbiomac.2021.06.014
23. Rezaei S, Kashanian S, Bahrami Y, Cruz LJ, Motiei M (2020) Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles
for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone Delivery. Molecules. 25:1181.
https://doi.org/10.3390/molecules25051181
24. Hong Y, Che S, Hui B, Yang Y, Wang X, Zhang X, Qiang Y, Ma H (2019) Lung cancer therapy using doxorubicin and curcumin combination:
targeted prodrug based, pH sensitive nanomedicine. Biomed Pharmacother. 112:108614. https://doi.org/10.1016/j.biopha.2019.108614
25. Hassanpour A, Irandoust M, Soleimani E, Zhaleh H (2019) Increasing the anticancer activity of azidothymidine toward the breast cancer via
rational design of magnetic drug carrier based on molecular imprinting technology. Mater Sci Eng C. 103:109771.
https://doi.org/10.1016/j.msec.2019.109771
26. Kurniawan DW, Fudholi A, Susidarti RA (2015) Synthesis of thiolated chitosan as matrix for the preparation of metformin hydrochloride
microparticles. Research in Pharmacy. 2:
27. Arif M, Dong Q-J, Raja MA, Zeenat S, Chi Z, Liu C-G (2018) Development of novel pH-sensitive thiolated chitosan/PMLA nanoparticles for
amoxicillin delivery to treat Helicobacter pylori. Mater Sci Eng C. 83:17-24. https://doi.org/10.1016/j.msec.2017.08.038
28. Bhatta A, Krishnamoorthy G, Marimuthu N, Dihingia A, Manna P, Biswal HT, Das M, Krishnamoorthy G (2019) Chlorin e6 decorated
doxorubicin encapsulated chitosan nanoparticles for photo-controlled cancer drug delivery. Int J Biol Macromol. 136:951-61.
https://doi.org/10.1016/j.ijbiomac.2019.06.127
29. Kahdestani SA, Shahriari MH, Abdouss M (2021) Synthesis and characterization of chitosan nanoparticles containing teicoplanin using sol–
gel. Polym. 78:1133-48.https://doi.org/10.1007/s00289-020-03134-2
30. Zare M, Samani SM, Sobhani Z (2018) Enhanced intestinal permeation of doxorubicin using chitosan nanoparticles. Adv Pharm Bull. 8:411.
https://doi.org/10.15171/apb.2018.048
31. Katuwavila NP, Perera A, Samarakoon SR, Soysa P, Karunaratne V, Amaratunga GA, Karunaratne D (2016) Chitosan-alginate nanoparticle system efficiently delivers doxorubicin to MCF-7 cells. J Nanomater. 2016:
32. El-Ghaffar A, Ahmed M, Akl MA-A, Kamel AM, Hashem MS (2017) Amino acid combined chitosan nanoparticles for controlled release of
doxorubicin hydrochloride. Egypt J Chem. 60:507-18. https://doi.org/10.21608/ejchem.2017.745.1021
33. Huang P-W, Zeng Z-W, Zheng W, Wang H, Wei X-H, Shi S-L (2022) Synthesis, Preparation and Evaluation of Doxorubicin-Loaded Chitosan
Oligosaccharide/Indomethacin Nanoparticles. J Clust Sci. 33:795-808. https://doi.org/10.1007/s10876-021-02017-4
34. Di Martino A, Kucharczyk P, Capakova Z, Humpolicek P, Sedlarik V (2017) Chitosan-based nanocomplexes for simultaneous loading, burst
reduction and controlled release of doxorubicin and 5-fluorouracil. Int J Biol Macromol. 102:613-24.
https://doi.org/10.1016/j.ijbiomac.2017.04.004
35. Pornpitchanarong C, Rojanarata T, Opanasopit P, Ngawhirunpat T, Patrojanasophon P (2020) Catechol-modified chitosan/hyaluronic acid
nanoparticles as a new avenue for local delivery of doxorubicin to oral cancer cells. Colloids Surf B. 196:111279.
https://doi.org/10.1016/j.colsurfb.2020.111279
36. Alkholief M (2019) Optimization of LecithinChitosan nanoparticles for simultaneous encapsulation of doxorubicin and piperine. J
Drug Deliv Sci Technol. 52:204-14.https://doi.org/10.1016/j.jddst.2019.04.012
37. Espinosa-Cano E, Huerta-Madroñal M, CámaraSánchez P, Seras-Franzoso J, Schwartz S, Abasolo I, San Román J, Aguilar MR (2021)
Hyaluronic acid (HA)-coated naproxennanoparticles selectively target breast cancer stem cells through COX-independent pathways.
Mater Sci Eng C. 124:112024.http://dx.doi.org/10.1016/j.msec.2021.112024
38. Qiu L, Ge L, Long M, Mao J, Ahmed KS, Shan X, Zhang H, Qin L, Lv G, Chen J (2020) Redoxresponsive biocompatible nanocarriers based on
novel heparosan polysaccharides for intracellular anticancer drug delivery. Asian journal of pharmaceutical sciences. 15:83-94.
https://doi.org/10.1016/j.ajps.2018.11.005
39. Xia D, Wang F, Pan S, Yuan S, Liu Y, Xu Y (2021) Redox/pH-Responsive Biodegradable Thiol-Hyaluronic Acid/Chitosan ChargeReversal Nanocarriers for Triggered Drug Release. Polymer. 13:3785. https://doi.org/10.3390/polym1321378540. Sun C, Lu J, Wang J, Hao P, Li C, Qi L, Yang L, He B, Zhong Z, Hao N (2021) Redox-sensitive polymeric micelles with aggregation-induced emission for bioimaging and delivery of
anticancer drugs. J Nanobiotechnology. 19:1-15.https://doi.org/10.1186/s12951-020-00761-9
41. Amer Ridha A, Kashanian S, Rafipour R, Hemati Azandaryani A, Zhaleh H, Mahdavian E (2021) A promising dual-drug targeted delivery system in cancer therapy: nanocomplexes of folate–apoferritin-conjugated cationic solid lipid nanoparticles. Pharm Dev Technol. 26:673-81.
https://doi.org/10.1080/10837450.2021.1920037
42. Edelman R, Assaraf YG, Levitzky I, Shahar T, Livney YD (2017) Hyaluronic acid-serum albumin conjugate-based nanoparticles for
targeted cancer therapy. Oncotarget. 8:24337.https://doi.org/10.18632/oncotarget.15363
43. Yassemi A, Kashanian S, Zhaleh H (2020) Folic acid receptor-targeted solid lipid nanoparticles to enhance cytotoxicity of letrozole through
induction of caspase-3 dependent-apoptosis for breast cancer treatment. Pharm Dev Technol. 25:397-407.
https://doi.org/10.1080/10837450.2019.1703739
44. Pan Y, Guo M, Nie Z, Huang Y, Peng Y, Liu A, Qing M, Yao S (2012) Colorimetric detection of apoptosis based on caspase-3 activity assay using unmodified gold nanoparticles. Chem comm. 48:997-9. https://doi.org/10.1039/C1CC15407A
https://doi.org/10.1016/j.sjbs.2022.103298
2. Wang C, Zhang Z, Chen B, Gu L, Li Y, Yu S (2018) Design and evaluation of galactosylated chitosan/graphene oxide nanoparticles as a drug
delivery system. J Colloid Interface Sci. 516:332- 41. https://doi.org/10.3390/polym14112287
3. Wang S-Y, Hu H-Z, Qing X-C, Zhang Z-C, Shao Z-W (2020) Recent advances of drug delivery nanocarriers in osteosarcoma treatment. J Cancer.11:69-82. https://doi.org/10.7150/jca.36588
4. Bajracharya R, Song JG, Patil BR, Lee SH, Noh H-M, Kim D-H, Kim G-L, Seo S-H, Park J-W, Jeong SH, Lee CH, Han H-K (2022) Functional
ligands for improving anticancer drug therapy: current status and applications to drug delivery systems. Drug Deliv. 29:1959-70.
https://doi.org/10.1080/10717544.2022.2089296
5. Chiesa E, Greco A, Riva F, Dorati R, Conti B, Modena T, Genta I (2022) CD44-Targeted Carriers: The Role of Molecular Weight of
Hyaluronic Acid in the Uptake of Hyaluronic Acid-Based Nanoparticles. Pharmaceuticals. 15:103. https://doi.org/10.3390%2Fph15010103
6. Vodyashkin AA, Kezimana P, Vetcher AA, Stanishevskiy YM (2022) Biopolymeric Nanoparticles–Multifunctional Materials of the
Future. Polymer. 14:2287. https://doi.org/10.3390/polym14112287
7. Jesus S, Marques AP, Duarte A, Soares E, Costa JP, Colaço M, Schmutz M, Som C, Borchard G, Wick P, Borges O (2020) Chitosan
Nanoparticles: Shedding Light on Immunotoxicity and Hemocompatibility. Front Bioeng Biotechnol. 8:100.
https://doi.org/10.3389/fbioe.2020.00100
8. George D, Maheswari PU, Begum KMS (2020) Cysteine conjugated chitosan based green nanohybrid hydrogel embedded with zinc oxide
nanoparticles towards enhanced therapeutic potential of naringenin. React Funct Polym. 148:104480.
http://dx.doi.org/10.1016/j.reactfunctpolym.2020.104480
9. M. Ways TM, Lau WM, Khutoryanskiy VV (2018) Chitosan and Its Derivatives for Application in Mucoadhesive Drug Delivery Systems. Polymer.10:267.https://doi.org/10.3390%2Fpolym10030267
10. Hershberger KK, Gauger AJ, Bronstein LM (2021) Utilizing Stimuli Responsive Linkages to Engineer and Enhance Polymer NanoparticleBased Drug Delivery Platforms. ACS Appl Bio Mater. 4:4720-36. https://doi.org/10.1021/acsabm.1c00351
11. Majumder J, Minko T (2021) Multifunctional and stimuli-responsive nanocarriers for targeted therapeutic delivery. Expert Opin Drug Deliv.
18:205-27.https://doi.org/10.1080/17425247.2021.1828339
12. Murugan B, Sagadevan S, Fatimah I, Oh W-C, Hossain MAM, Johan MR (2021) Smart stimuliresponsive nanocarriers for the cancer therapy –
nanomedicine. Nanotechnol Rev. 10:933-53.https://doi.org/10.1515/ntrev-2021-0067
13. Xiang Z, Liu M, Song J (2021) StimuliResponsive Polymeric Nanosystems for Controlled Drug Delivery. Appl Sci. 11:9541.
https://doi.org/10.3390/app11209541
14. Omrani I, Babanejad N, Shendi HK, Nabid MR (2017) Fully glutathione degradable waterborne polyurethane nanocarriers: Preparation, redoxsensitivity, and triggered intracellular drug release. Mater Sci Eng C. 70:607-16. http://dx.doi.org/10.1016/j.msec.2016.09.036
15. Yap WF, Yunus WMM, Yusof NA, Ibrahim NI, Zainudin AA. Characterization and optical properties of L-cysteine/chitosan biocomposite
thin film. 2014.
16. Butowska K, Woziwodzka A, Borowik A, Piosik J (2021) Polymeric Nanocarriers: A Transformation in Doxorubicin Therapies.
Materials (Basel, Switzerland).
14:https://doi.org/10.3390/ma14092135
17. Wang D, Zhang X, Xu B (2021) PEGylated Doxorubicin Prodrug-Forming ReductionSensitive Micelles With High Drug Loading and
Improved Anticancer Therapy. Front Bioeng Biotechnol. 9:https://doi.org/10.3389/fbioe.2021.781982
18. Tan ML, Choong PF, Dass CR (2009) Doxorubicin delivery systems based on chitosan for cancer therapy. J Pharm Pharmacol. 61:131-
42. https://doi.org/10.1211/jpp.61.02.0001
19. Shakil MS, Mahmud KM, Sayem M, Niloy MS,Halder SK, Hossen MS, Uddin MF, Hasan MA (2021) Using Chitosan or Chitosan Derivatives in
Cancer Therapy. Polysaccharides. 2:795-816.https://doi.org/10.3390/polysaccharides204004820. Mazzotta E, De Benedittis S, Qualtieri A,
Muzzalupo R (2019) Actively targeted and redox responsive delivery of anticancer drug by chitosan nanoparticles. Pharmaceutics. 12:26.
https://doi.org/10.3390%2Fpharmaceutics12010026
21. A. B-S, M.D. H, C.E. K, N. L (2002) Thiolated polymers: Stability of thiol moieties under different storage conditions. Sci Pharm. 70:331-
9. https://doi.org/10.3797/scipharm.aut-02-32
22. Helmi O, Elshishiny F, Mamdouh W (2021) Targeted doxorubicin delivery and release within breast cancer environment using PEGylated
chitosan nanoparticles labeled with monoclonal antibodies. Int J Biol Macromol. 184:325-38. https://doi.org/10.1016/j.ijbiomac.2021.06.014
23. Rezaei S, Kashanian S, Bahrami Y, Cruz LJ, Motiei M (2020) Redox-Sensitive and Hyaluronic Acid-Functionalized Nanoparticles
for Improving Breast Cancer Treatment by Cytoplasmic 17α-Methyltestosterone Delivery. Molecules. 25:1181.
https://doi.org/10.3390/molecules25051181
24. Hong Y, Che S, Hui B, Yang Y, Wang X, Zhang X, Qiang Y, Ma H (2019) Lung cancer therapy using doxorubicin and curcumin combination:
targeted prodrug based, pH sensitive nanomedicine. Biomed Pharmacother. 112:108614. https://doi.org/10.1016/j.biopha.2019.108614
25. Hassanpour A, Irandoust M, Soleimani E, Zhaleh H (2019) Increasing the anticancer activity of azidothymidine toward the breast cancer via
rational design of magnetic drug carrier based on molecular imprinting technology. Mater Sci Eng C. 103:109771.
https://doi.org/10.1016/j.msec.2019.109771
26. Kurniawan DW, Fudholi A, Susidarti RA (2015) Synthesis of thiolated chitosan as matrix for the preparation of metformin hydrochloride
microparticles. Research in Pharmacy. 2:
27. Arif M, Dong Q-J, Raja MA, Zeenat S, Chi Z, Liu C-G (2018) Development of novel pH-sensitive thiolated chitosan/PMLA nanoparticles for
amoxicillin delivery to treat Helicobacter pylori. Mater Sci Eng C. 83:17-24. https://doi.org/10.1016/j.msec.2017.08.038
28. Bhatta A, Krishnamoorthy G, Marimuthu N, Dihingia A, Manna P, Biswal HT, Das M, Krishnamoorthy G (2019) Chlorin e6 decorated
doxorubicin encapsulated chitosan nanoparticles for photo-controlled cancer drug delivery. Int J Biol Macromol. 136:951-61.
https://doi.org/10.1016/j.ijbiomac.2019.06.127
29. Kahdestani SA, Shahriari MH, Abdouss M (2021) Synthesis and characterization of chitosan nanoparticles containing teicoplanin using sol–
gel. Polym. 78:1133-48.https://doi.org/10.1007/s00289-020-03134-2
30. Zare M, Samani SM, Sobhani Z (2018) Enhanced intestinal permeation of doxorubicin using chitosan nanoparticles. Adv Pharm Bull. 8:411.
https://doi.org/10.15171/apb.2018.048
31. Katuwavila NP, Perera A, Samarakoon SR, Soysa P, Karunaratne V, Amaratunga GA, Karunaratne D (2016) Chitosan-alginate nanoparticle system efficiently delivers doxorubicin to MCF-7 cells. J Nanomater. 2016:
32. El-Ghaffar A, Ahmed M, Akl MA-A, Kamel AM, Hashem MS (2017) Amino acid combined chitosan nanoparticles for controlled release of
doxorubicin hydrochloride. Egypt J Chem. 60:507-18. https://doi.org/10.21608/ejchem.2017.745.1021
33. Huang P-W, Zeng Z-W, Zheng W, Wang H, Wei X-H, Shi S-L (2022) Synthesis, Preparation and Evaluation of Doxorubicin-Loaded Chitosan
Oligosaccharide/Indomethacin Nanoparticles. J Clust Sci. 33:795-808. https://doi.org/10.1007/s10876-021-02017-4
34. Di Martino A, Kucharczyk P, Capakova Z, Humpolicek P, Sedlarik V (2017) Chitosan-based nanocomplexes for simultaneous loading, burst
reduction and controlled release of doxorubicin and 5-fluorouracil. Int J Biol Macromol. 102:613-24.
https://doi.org/10.1016/j.ijbiomac.2017.04.004
35. Pornpitchanarong C, Rojanarata T, Opanasopit P, Ngawhirunpat T, Patrojanasophon P (2020) Catechol-modified chitosan/hyaluronic acid
nanoparticles as a new avenue for local delivery of doxorubicin to oral cancer cells. Colloids Surf B. 196:111279.
https://doi.org/10.1016/j.colsurfb.2020.111279
36. Alkholief M (2019) Optimization of LecithinChitosan nanoparticles for simultaneous encapsulation of doxorubicin and piperine. J
Drug Deliv Sci Technol. 52:204-14.https://doi.org/10.1016/j.jddst.2019.04.012
37. Espinosa-Cano E, Huerta-Madroñal M, CámaraSánchez P, Seras-Franzoso J, Schwartz S, Abasolo I, San Román J, Aguilar MR (2021)
Hyaluronic acid (HA)-coated naproxennanoparticles selectively target breast cancer stem cells through COX-independent pathways.
Mater Sci Eng C. 124:112024.http://dx.doi.org/10.1016/j.msec.2021.112024
38. Qiu L, Ge L, Long M, Mao J, Ahmed KS, Shan X, Zhang H, Qin L, Lv G, Chen J (2020) Redoxresponsive biocompatible nanocarriers based on
novel heparosan polysaccharides for intracellular anticancer drug delivery. Asian journal of pharmaceutical sciences. 15:83-94.
https://doi.org/10.1016/j.ajps.2018.11.005
39. Xia D, Wang F, Pan S, Yuan S, Liu Y, Xu Y (2021) Redox/pH-Responsive Biodegradable Thiol-Hyaluronic Acid/Chitosan ChargeReversal Nanocarriers for Triggered Drug Release. Polymer. 13:3785. https://doi.org/10.3390/polym1321378540. Sun C, Lu J, Wang J, Hao P, Li C, Qi L, Yang L, He B, Zhong Z, Hao N (2021) Redox-sensitive polymeric micelles with aggregation-induced emission for bioimaging and delivery of
anticancer drugs. J Nanobiotechnology. 19:1-15.https://doi.org/10.1186/s12951-020-00761-9
41. Amer Ridha A, Kashanian S, Rafipour R, Hemati Azandaryani A, Zhaleh H, Mahdavian E (2021) A promising dual-drug targeted delivery system in cancer therapy: nanocomplexes of folate–apoferritin-conjugated cationic solid lipid nanoparticles. Pharm Dev Technol. 26:673-81.
https://doi.org/10.1080/10837450.2021.1920037
42. Edelman R, Assaraf YG, Levitzky I, Shahar T, Livney YD (2017) Hyaluronic acid-serum albumin conjugate-based nanoparticles for
targeted cancer therapy. Oncotarget. 8:24337.https://doi.org/10.18632/oncotarget.15363
43. Yassemi A, Kashanian S, Zhaleh H (2020) Folic acid receptor-targeted solid lipid nanoparticles to enhance cytotoxicity of letrozole through
induction of caspase-3 dependent-apoptosis for breast cancer treatment. Pharm Dev Technol. 25:397-407.
https://doi.org/10.1080/10837450.2019.1703739
44. Pan Y, Guo M, Nie Z, Huang Y, Peng Y, Liu A, Qing M, Yao S (2012) Colorimetric detection of apoptosis based on caspase-3 activity assay using unmodified gold nanoparticles. Chem comm. 48:997-9. https://doi.org/10.1039/C1CC15407A
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Mar 26, 2023
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Mahsa Babaei, Soheila Kashanian, Zahra Salemi, & Hossein Zhaleh. (2023). Redox-Sensitive Targeted Doxorubicin-Loaded Chitosan-based Nanoparticles to Treat Breast Cancer. Journal of Population Therapeutics and Clinical Pharmacology, 30(4), 267–282. https://doi.org/10.47750/jptcp.2023.30.04.026
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