TONG HOP PHlTC CHAT PAMAIM DENDRIMER - Pt^^
Nguvin Ciiii Khoa ', Nguyen Anh Tuan ^, Hoang Thi Kim Dung 'Vien Cong nghe hoa hoc - Vien Khoa hoc va Cong nghe Viet Nam
Truong Dai hoc Can Tho"
Email: nckhoavnn(g),vahoo.com Abstract:
In this article, we provide a detailed procedure of the synthesis of t,vo poly(amidoamin) dendrimer/Pt complexes, by using poly(amidoamin)
dendrimer second and third-generation with core elhylendiamine (EDA) and potassium telrachloroplalinale(II) (K2P1CI4). The products M'ere characterized by
UV - vis, IR, Ramam spectroscopy and ICP-AES (Inductively coupled plasma atomic emission spectroscopy). The results of antiproliferative activity testing on NCI-H460 cell line show that G2.0-Pl and G3.0-Pl complexes have much stronger aelivily than G2.0, G3.0 andK2P1CI4.
Tom tat:
Tit dendrimer polyamidoamine (PAMAM) vdi core ethylenediamine (EDA) thi hi 2,0 vd 3,0 vd potassium telrachloroplatinate(II) (K2PtCl4), hai phirc PAMAM/Pr* dd dugc tdng hgp. Cdu tnic cdc phitc ndy dd dugc xdc dinh bdng phd UV-Vis, IR, Raman vd ICP-AES. Kit qud thu nghiim khd ndng chdng tdng sinh li bdo Irin ddng ti bdo ung thu phdi NCI-H460 cho thdy cdc phirc G2.0-Pt vd G3.0-Pl cd hoai Hnh manh han PAMAM G2.0, G3.0 vd K2P1CI4.
I - MO DAU
Cac phirc chat ciia platinum nhu cis-diammindichloroplatinum(ll) (cisplatin, cis- [PtCl2(NH3)2]) , trans-[PtCl2(NH3)2] va mpt sd hgp chat plahnum khac da dugc iing dyng trong dieu tri ung thu: ung thu tinh hoan, ung thu budng trim^, ung thu phdi.. .[1] Tuy nhien, cac hgp chat platin thudng cd nhieu tac dung phy nen da cd nhieu nghien cim de giam cac tac dyng phy nay nhu phdi hgp vdi mdt vai loai tbudc. gan tren chat mang de kiem soat thdi gian phdng thich thude... Trong dd, cd mdt sd nghien cim gan cac hgp chat platin len dendrimer nhu PAMAM de tao ra cac hop chat mdi cd kha nang tan tdt, ban che lieu dimg va dap img tbudc tdt hon [2].
Trong bai bao nay, chiing tdi se de cap den qua trinh tdng hop hai phirc PAMAM/Pt^^ tir dendrimer polyamidoamine (PAMAM) vdi core ethylenediamine (EDA) the he 2,0 va 3,0 va potassium tetrachloroplatinate(II) (K2PtCl4).
II - THUC NGHIEM 1. Nguyen lieu:
PAMAM the he 2,0 va 3,0 dugc tdng hgp tai Phdng Cdng nghe bun ca polymer - Vien Cdng nghe Hda hpc theo tai lieu tham khao [4].
KjPtCU-Merck.
2. Phuong phap tong hop phiic PAMAM dendrimer voi Pt^^ . Tdng hop phirc PAMAM dendrimer G2.0/Pt^"^ (ki hieu la PI)
Lay 0,05 mmoL (0,0208 g) mudi K2PtCl4 hda tan trong 4 mL H2O khuiy lien tyc trong 4 gid d nhiet dp thudng.
Tiiu ban: Khoa hoc Vdt lieu ISBN: 978-604-913-011-
Liy 0,0042 mmoL (0,0136 g) dung dich PAMAM dendrimer thi he G 2.0 core EDA. hda tan trong 1 mL dung dich methanol, khuay nira gid d nhiet dp thudng trong khi N2.
Cho tir tir dd K2PtCl4 vao dd PAMAM, khuiy hon hpp phan ung d nliipt dp thudng trong mdi tmdng khi N2, sau khoang 1 gid thay ket tiia vang nhat xuat hien. Tiep tyc khuay them hdn hgp phan img khoang 23 gid cho phan iing dien ra hoan toan. Ly tam va rira sach nhieu lan bang nude, tach lay san pham, say.
Tdng hap phirc PAMAM dendrimer G3.0/Pt^"' (ki hieu la P2)
Liy 0,05 mmoL (0,0208 g) muli K2PtCl4 hda tan trong 4 mL HiO khuiy lien tyc trong 4 gid d nhiet dp thudng.
Liy 0,0021 mmoL (0,0144 g) dung dich PAMAM dendrimer thi he G3.0 core EDA, hda tan trong 1 mL dung dich methanol, khuay nira gid d nhiet dp thudng trong khi N2.
Cho tir tir dd K2PtCl4 vao dd PAMAM, khuay dung dich phan ung d nhiet dp thudng trong mdi tmdng khi N2, sau nira gid thay ket tiia vang nhat xuat hien. Tiep tyc khuay them hdn hgp phan ling khoang 23 gid cho phan img dien ra hoan toan. Ly tam va rira sach nhieu lan bang nude, tach san pham, say khd san pham.
Ham lugng Pt dugc xac dinh bing phuang phap ICP-AES tai Trung tam dich vy phan tich thanh phi H I Chi Minh. Phd UV - vis dugc do tren mav UV - 2450 - Shimadzu. Phd IR do d dang vien nen vdi KBr vdi tan sd chay 400 - 4000 cm " tai Vien Khoa hpc Vat lieu irng dyng.
Pho Raman do vdi ngudn hire xa tir laser Heli - Neon X = 6328 A° d budc sdng tir 300 - 600 cm"' tai Dai Hpc Qudc Gia Hd Chi Minh.
3. Phuong phap thir boat tinh gay doc te bao: (thyc hien tai Phong Sinh hpc phan tir, Khoa Sinh, Tmdng Dai hpc Khoa hpc Ty nhien Tp.HCM) [3]
Phuong phap Sulforhodamine B (SRB): diing de danh gia kha nang gay dpc te bao cua tac nhan nghien cim. Thir nghiem dua vao kha nang ciia SRB, la tbudc nhupm aminoxanthene mau hdng sang vdi hai nhdm sulfonic gan tinh dien vdi protein ciia eae te bao sau khi dugc cd dinh bang TCA (trichloroacetic acid). Te bao dugc nudi trong dia 96 gieng. Sau khi ii 24 gid, te bao dugc xir ly vdi tbudc d nhirng ndng dp khac nhau trong 48 gid. Sau dd, te bao dugc cd dinh bang TCA 50% va nhupm vdi SRB 0.2%. Tdng lugng protein te bao dugc nhupm phan anh sd lugng te bao sdng sau khi xir ly vdi boat chat, va dugc danh gia bang phuong phap do mat dp quang (OD) d budc sdng 492 nm.
Ill - KET QUA VA THAO LUAN 1- Tong hgp phuc PAMAM dendrimer voi Pt^^
"iK
/ "-' S,.-'' ,.•••' ••••.. \ r '^ \
„ v , ; M , , . N> C'6'HE f ' f i : '• 9, :
"'V-.^'(,A..^-,/^'-.,° °,/'^„''.Oi-r
G -0 5
Khi cho PAMAM dendrimer vdi K2PtCl4 thi phan irng xay ra theo sa do sau:
P o
11 ^ C H 2 " C H 2 ~ N H 2 c _^C H CH2-CH2-NH2
R ^ + K j P t C U
?\~~~H—CH2-CH2-NH2
o
Ket qua phan tich pho UV - vis (hinh 2):
- ^ R '
ff-
o
- C H 2 - C H 2 - N H 2 / • 'Cl
2000
, 0 0 0
0000
^ " l
\ \ \
1
*
— _ _ - L - ^ ^
• "
Mxa
0300
0.000
1
i
"'• "^--. ^ 1
Hinh 2; Phd UV cita cdc hgp chdt
a) Phd UV-vis cua K2PtCl4 b) PAMAM dendrimer G2.0 c) Phitc G2.0/Pt^^
Dua vao sy khac biet ciia phd UV - vis cho thay da gan dugc kim loai Platin vao PAMAM dendrimer. Ca hai phirc PI va P2 deu cd peak d 260 ^ 275 nm va dac biet cd mgt peak manh d 200 -^ 230 nm dac tnmg cho chuyen miic kem chuyen dien tich tir phdi tir clo den ion trung tam Pt (II) [8].
De thay dugc cac dao dgng dac trung cho lien ket Pt - phdi tir, ngoai phd IR, chiing tdi da ghi phd Raman ciia tac chat PAMAM dendrimer va san pham phiic tuong iing. Ket qua dugc trinh bay d bang 1.
Bdng I; Cdc vdn hdp thu chinh trin phd dao ddng cua cdc chdt nghiin ciru, cm'
Chit PAMAM G2.0
P I
PAMAM G3.0
P2
Phd IR Raman
IR Raman
IR Raman
IR Raman
vc=o 1680, 1630
1731, 1646
1680,1646
1660, 1650
VNH (amin)
1458, 1363
1379,1272
1558,1460
1552,1449
Vc-N(amit)
1196, 1121
1122, 1071
1361, 1125
1253, 1061
Vpt-N
0 0 0 430,560
0 0 0 425,575
Tiiu ban Khoa hoc viit lieu ISBN: 978-604-913-011-3
Cd the quan sat thay sy tang tan sd hap thy ciia vc=o d hai phirc PI. P2 ciing \'di sy giam tan sd dao dpng bien dang cua VNH, dao dpng keo cang ciia VCN d hai phirc PI. P2 [5].
Ngoai ra tren phd Raman ciia phiic PI, P2 cd xuit hien peak d 430 - 580 cm"' dac trung cho dao dpng hda tri Pt-N [6]. Deu dd chiing td cd sy tao phirc ciia cac PAMAM vdi Pt(II) va su tao phirc dugc thyc hien qua nguyen tir nita ciia PAMAM dendrimer [7].
Xac dinh ham lupng platinum tren cac phiic PI, P2 theo phuang phap ICP va dat ket qua nhu sau:
Phiic PI P2
Ham lupng Platinum (mg/g) 379
395 2. Ket qua thu kha nang gay doc te bao:
Ket qua khao sat tren ddng tl bao ung thu phii NCI-H460, sang Ipc d ndng dp 100 pg/mL.
STT
1 2 3 4 5
Mau
G3.0 + Pt^^
G2.0 + Pt^^
G3.0 G2.0 K2PtCl4
Ti le (%) gay doe te bao Lan 1
77.90 80.18 10.59 4.67 49.38
Lan 2 77.34 77.19 0.82 -7.52 47.71
Lan 3 77.23 77.20 3.55 -1.50 50.84
TB ± DEC
(trung binh ± dp lech chuan) 77.23 ±0.73
78.19± 1.73 4.99 ±5.04 -1.45 ±6.09 49.31 ± 1.57
Ket qua cho thay cac hgp chat tdng hgp dugc cd kha nang gay ddc te bao manh ban K2PtCl4 va cac dendrimer ban dau.
IV - KET LUAN
Hai phiic PAMAM/Pt (G2,0 va G3,0) da dugc tdng hgp. Cau true cac phirc nay da J.+
dugc xac dinh bang phd UV-Vis, IR, Raman va ICP-AES. Kit qua thir nghiem kha nang chdng tang sinh te bao tren ddng tl bao ung thu phdi NCI-H460 cho thiy cac phirc G2.0-Pt va G3.0-Pt cd boat tinh manh ban PAMAM G2.0, G3.0 va K2PtCl4.
TAI LIEU THAM KHAO
1. Bemhard Lippert (Ed.). Cis platin Chemistry and Biochemistry of a Leading Anticancer Drug, Veriag Helvehca Chi- mica Acta, Zurich. 1999, p. 479.
2. Bob A. Howell, Daming Fan, and Leela Rakesh, Nanoscale dendrimer-platinum
3. Hd Huynh Thiiy Duong, Bdo cdo idng kit di tdi Xdy dung vd hodn chinh cdc quy trinh diing trong sdng lgc tinh khdng phdn bdo ciia cdy thude a mirc do li bdo vd phdn tu, Chuong trinh Nghien cim co ban, Sd Khoa hpc va Cdng nghe Tp.HCM 2007.
4. Nguyen Cim Khoa, Hoang Thi Kim Dung, Tdng hgp cdc dendrimer polyamidoamine (PAMAM), Tap chi Hda hpc 47, 4A. 123-126, 2009.
5. Nguyen Hum Dinh, Tran Thi Da, lfng dung mdt sd phircmg phdp phd nghien ciru cdu true phdn tu, NXB giao dye - 1999.
6. Nguyen Thanh Hdng, Cdc phucmg phdp phd trong hda hgc hiru ca. NXB khoa hpc va ky thuat, 2007.
7. Nguyen Thi Thanh Chi, Tran Thi Da, Vii Quang Nhu, Nguyen Hun Dinh, Tdng hgp va cau tnic ciia mgt sd phirc chat trans(dichloro(safral)(amin thom) platin(II), Tap chi Hda hpc, T.45 (2), Tr. 176 - 180, 2007.
8. Tran Thi Da, Nguyen Cao Cudng, Nguyen Hiru Dinh, Tdng hgp, cdu trite vd tinh chdt mot vdi phuc chdt cua platin (II) chua pyridin vd toluidin hode anizidin. Tap chi Hda hpc, T. 43 (4), Tr. 442 - 446 (2005).
Tiiu ban Khoa hoc vdt lieu ISBN: 978-604-913-1" ' ' 3
MOT SO LTNG DUNG TRONG Y SINH VA MOI TRlTONG CUA CHITOSAN
Tran Dai Lam' *, Pham Gia Dien^*, Nguyin Xuan Phiic'*, Nguyen Hai Binh', Mai Thu Trang', Nguyen Thj Ngoan^ Ha Phuong Thu', Pham H6ng Nam', Phan Thi Bich Hoa',
Le Quang Duong', VQ Thi Hoa'
1 - Phdng vat lieu Nano Y sinh, Vien Klioa hpc vat lieu 2- Phdng Cdng nghe cac chat cd boat tinh sinh hpc, Vien hda hpc
Email: tdlamfojvast.ac.vn Tom tat:
Bdi bdo Irinh bdy Idng quan cdc kit qud nghien ciru vd irng dung cua chitosan trong y sinh hgc (chi tga gdm y sinh nhdn tgo, chi tgo hi ddn ihudc nano, nhiit tri ung thu) vd xir ly mdi trudng (hdp phu kim logi ndng. khdng khudn);
chUgsgn/chUin Id mdt polysacarit mgch thdng cd ngudn gdc thien nhiin, ed tinh tuang thich sinh hgc egg. Ngno chilosgn citng dugc nghiin ciru -phdt triin thdnh hi ddn ihudc irng dung trong diiu tri nhu cucurmin chua ung thu, hgt nano tir trong nhiit Iri. Trong linh vuc xir ly mdi trirdng, cdc vdt lieu nano (hgt nano tir, hat nano bgc...) dugc pha tgp vdo chitosan di Idng khd ndng hdp phu kim logi ndng vd khdng khudn, khdng li bdo. Cdc kit qud nghiin citu dd chitng Id vdt lieu chitosan cd nhiiu tiim ndng ung dung Irongy sinh hgc vd xu ly mdi trudng.
Abstract:
This paper review's some results and applications of chitosan such as artificial bone preparation, drug delivery system, hyperthermia for cancer and environmental treatment (heavy metals adsorption, aniibacleria). Chitin and chitosan are natural polysaccharide and both have a high biocompalibility.
Artificial bone M'OS successfully fabricated based on chitosan/hydroxyapatite materials. Next, nano chitosan particles were developed lo make drug carrier for curcumin deliveiy (as cancer treatment). Nano magnetic particles/chUosan was also used in hyperthermia experiment For environmental field, nano magnetic particles, and chitosan- based silver particles were expected lo help increase heavy metal absorbability and antibacterial activity respectively. Briefiy, it was shown that chitosan materials had numerous promising applicalions in biomedical and environmental field.
I. Gioi thieu:
Chitosan/ chitin la mdt polisacarit mach thing, cd ngudn glc ty nhien, tap trung nhieu trong vd cac loai thuy san giap xac nhu tdm, cua, mai myc. Nd cd kha nang hda hgp va ly phan buy sinh hpc. ddc tinh thap, hoatjinh sinh hpc cao va da dang nhu : khang khuin, khang nam. tang sinh te bao. tang cudng mien dich cua co thi vdi cac tac dyng kich thich san sinh bach cau. giam cholesterol trong mau, ban chi sy phat triln cua khdi u, cd tac dung tot tren cac vet thuang \'et bdng [1-4]. Viec img dyng chitosan trong cac linh vyc y sinh nhu cbl tao gdm y sinh [5] hoac he dan tbudc nano [6] hay xir ly mdi trudng [3,7-8] da dugc phat triln manh me. Trong bai bao nay, chiing tdi trinh bay tong quan cac kit qua nghien ciai irng dung cua chitosan trong y sinh (ehl tao he din thuoc, hieu img nhiet tri...) va xir ly mdi trudng
