Abstract
Doxorubicin (DOX) is commonly used to treat human malignancies, and its efficacy can be maximized by limiting the cardiac toxicity when combined with nanoparticles. Here, we reported a unique type of reversibly disulfide cross-linked micellar formulation of DOX (DOX-DCMs) for the targeted therapy of B-cell lymphoma. DOX-DCMs exhibited high drug loading capacity, optimal particle sizes (15-20 nm), outstanding stability in human plasma, and stimuli-responsive drug release profile under reductive conditions. DOX-DCMs significantly improved the pharmacokinetics of DOX, and its elimination half-life (t1/2) and area under curve (AUC) were 5.5 and 12.4 times of that of free DOX, respectively. Biodistribution studies showed that DOX-DCMs were able to preferentially accumulate in the tumor site and significantly reduce the cardiac uptake of DOX. In a xenograft model of human B-cell lymphoma, compared with the equivalent dose of free DOX and non-crosslinked counterpart, DOX-DCMs not only significantly inhibited the tumor growth and prolonged the survival rate, but also remarkably reduced DOX-associated cardiotoxicity. Furthermore, the exogenous administration of N-acetylcysteine (NAC) at 24 h further improved the therapeutic efficacy of DOX-DCMs, which provides a "proof-of-concept" for precise drug delivery on-demand, and may have great translational potential as future cancer nano-therapeutics.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 8207-8216 |
| Number of pages | 10 |
| Journal | Nanoscale |
| Volume | 10 |
| Issue number | 17 |
| DOIs | |
| State | Published - May 7 2018 |
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ASJC Scopus subject areas
- Materials Science(all)
Cite this
Reversibly disulfide cross-linked micelles improve the pharmacokinetics and facilitate the targeted, on-demand delivery of doxorubicin in the treatment of B-cell lymphoma. / Xiao, Kai; Liu, Qiangqiang; Al Awwad, Nasir; Zhang, Hongyong; Lai, Li; Luo, Yan; Lee, Joyce S; Li, Yuanpei; Lam, Kit.
In: Nanoscale, Vol. 10, No. 17, 07.05.2018, p. 8207-8216.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reversibly disulfide cross-linked micelles improve the pharmacokinetics and facilitate the targeted, on-demand delivery of doxorubicin in the treatment of B-cell lymphoma
AU - Xiao, Kai
AU - Liu, Qiangqiang
AU - Al Awwad, Nasir
AU - Zhang, Hongyong
AU - Lai, Li
AU - Luo, Yan
AU - Lee, Joyce S
AU - Li, Yuanpei
AU - Lam, Kit
PY - 2018/5/7
Y1 - 2018/5/7
N2 - Doxorubicin (DOX) is commonly used to treat human malignancies, and its efficacy can be maximized by limiting the cardiac toxicity when combined with nanoparticles. Here, we reported a unique type of reversibly disulfide cross-linked micellar formulation of DOX (DOX-DCMs) for the targeted therapy of B-cell lymphoma. DOX-DCMs exhibited high drug loading capacity, optimal particle sizes (15-20 nm), outstanding stability in human plasma, and stimuli-responsive drug release profile under reductive conditions. DOX-DCMs significantly improved the pharmacokinetics of DOX, and its elimination half-life (t1/2) and area under curve (AUC) were 5.5 and 12.4 times of that of free DOX, respectively. Biodistribution studies showed that DOX-DCMs were able to preferentially accumulate in the tumor site and significantly reduce the cardiac uptake of DOX. In a xenograft model of human B-cell lymphoma, compared with the equivalent dose of free DOX and non-crosslinked counterpart, DOX-DCMs not only significantly inhibited the tumor growth and prolonged the survival rate, but also remarkably reduced DOX-associated cardiotoxicity. Furthermore, the exogenous administration of N-acetylcysteine (NAC) at 24 h further improved the therapeutic efficacy of DOX-DCMs, which provides a "proof-of-concept" for precise drug delivery on-demand, and may have great translational potential as future cancer nano-therapeutics.
AB - Doxorubicin (DOX) is commonly used to treat human malignancies, and its efficacy can be maximized by limiting the cardiac toxicity when combined with nanoparticles. Here, we reported a unique type of reversibly disulfide cross-linked micellar formulation of DOX (DOX-DCMs) for the targeted therapy of B-cell lymphoma. DOX-DCMs exhibited high drug loading capacity, optimal particle sizes (15-20 nm), outstanding stability in human plasma, and stimuli-responsive drug release profile under reductive conditions. DOX-DCMs significantly improved the pharmacokinetics of DOX, and its elimination half-life (t1/2) and area under curve (AUC) were 5.5 and 12.4 times of that of free DOX, respectively. Biodistribution studies showed that DOX-DCMs were able to preferentially accumulate in the tumor site and significantly reduce the cardiac uptake of DOX. In a xenograft model of human B-cell lymphoma, compared with the equivalent dose of free DOX and non-crosslinked counterpart, DOX-DCMs not only significantly inhibited the tumor growth and prolonged the survival rate, but also remarkably reduced DOX-associated cardiotoxicity. Furthermore, the exogenous administration of N-acetylcysteine (NAC) at 24 h further improved the therapeutic efficacy of DOX-DCMs, which provides a "proof-of-concept" for precise drug delivery on-demand, and may have great translational potential as future cancer nano-therapeutics.
UR - http://www.scopus.com/inward/record.url?scp=85046676437&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046676437&partnerID=8YFLogxK
U2 - 10.1039/c8nr00680f
DO - 10.1039/c8nr00680f
M3 - Article
C2 - 29682647
AN - SCOPUS:85046676437
VL - 10
SP - 8207
EP - 8216
JO - Nanoscale
JF - Nanoscale
SN - 2040-3364
IS - 17
ER -