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Biomedical subjects

Chun Li

Publications and source records attributed to Chun Li.

At least 73 records · Page 4Linked to original sources

Imaging taxane-induced tumor apoptosis using PEGylated, 111In-labeled annexin V.

UNLABELLED: 99mTc-Labeled annexin V has been used for the imaging of tumor apoptosis induced by chemotherapy. However, owing to the short half-life of annexin V, multiple injections of the radiotracer are necessary to capture the peak apoptotic activity. In this study, we evaluated the imaging properties of an (111)In-labeled, long-circulating annexin V. METHODS: Both polyethylene glycol (PEG) and the metal chelator diethylenetriaminepentaacetic acid (DTPA) were simultaneously introduced to annexin V or ovalbumin through the use of a heterofunctional PEG precursor. Imaging studies were performed in mice bearing subcutaneously inoculated human mammary MDA-MB-468 tumors. The mice were treated with poly(L-glutamic acid)-paclitaxel, monoclonal antibody C225, or a combination of poly(L-glutamic acid)-paclitaxel and C225, followed by intravenous injection of (111)In-DTPA-PEG-annexin V. Images were acquired 48 h after the injection of the radiotracer. Autoradiography and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling) staining were performed on adjacent tumor slices for the localization of apoptotic cells. The imaging properties of unPEGylated annexin V and PEGylated ovalbumin were also determined to permit assessment of the specificity of (111)In-DTPA-PEG-annexin V. RESULTS: Tumor apoptotic index increased from 1.67% +/- 0.31% at baseline to 7.60% +/- 0.72% and 11.07% +/- 1.81%, respectively, 4 d after treatment with poly(L-glutamic acid)-paclitaxel or combined poly(L-glutamic acid)-paclitaxel and C225. Tumor uptake (percentage of injected dose per gram of tumor [%ID/g]) of PEGylated (111)In-DTPA-PEG-annexin 4 d after treatment was significantly higher in tumors treated with poly(L-glutamic acid)-paclitaxel (10.76 +/- 1.38 %ID/g; P = 0.001) and with combined poly(L-glutamic acid)-paclitaxel and C225 (9.84 +/- 2.51 %ID/g; P = 0.029) than in nontreated tumors (6.14 +/- 0.67 %ID/g), resulting in enhanced visualization of treated tumors. (111)In-DTPA-PEG-annexin V distributed into the central zone of tumors, whereas (111)In-DTPA-annexin V was largely confined to the tumor periphery. Furthermore, uptake of (111)In-DTPA-PEG-annexin V by tumors correlated with apoptotic index (r = 0.87, P = 0.02). Increase in tumor uptake of the nonspecific PEGylated protein (111)In-DTPA-PEG-ovalbumin was also observed after poly(L-glutamic acid)-paclitaxel treatment (55.6%), although this increase was less than that observed for (111)In-DTPA-PEG-annexin V (96.7%). CONCLUSION: Increased uptake of and improved visualization with (111)In-DTPA-PEG-annexin V in solid tumors after chemotherapy are mediated through both specific binding to apoptotic cells and nonspecific retention of macromolecular contrast agents in the tumors. (111)In-Labeled, PEGylated annexin V may be used to assess tumor response to chemotherapy.

Animals↗

Genetic polymorphisms in the IGFBP3 gene: association with breast cancer risk and blood IGFBP-3 protein levels among Chinese women.

Cumulative evidence suggests that insulin-like growth factors (IGF) play an important role in the etiology of breast cancer. The IGF binding proteins regulate the action of IGFs, and >90% of circulating IGFs are bound to IGFBP-3. We evaluated the associations of five (A-202C, G227C, C3804G, 5606InsA, and C5827T) genetic polymorphisms in the IGFBP3 gene with breast cancer risk and the blood IGFBP-3 protein level in a population-based, case-control study conducted among Chinese women in Shanghai. Genomic DNA samples from 1,193 incident breast cancer patients and 1,310 community controls were genotyped for IGFBP3 polymorphisms. Blood IGFBP-3 levels were determined for 390 controls. A 30% to 60% elevated risk of breast cancer was found to be associated with homozygosity for the variant allele in polymorphisms A-202C, G227C, 5606InsA, and C5827T. Carrying the variant allele in C3804G was also associated with an increased risk. About 13.5% of cases and 9.7% of controls had one or more of the above risk genotypes, resulting in odds ratio [OR; 95% confidence interval (95% CI)] of 1.4 (1.0-1.9). The ORs (95% CIs) were 1.3 (1.0-1.8) and 1.7 (1.1-2.5) for women with one to two and three to five risk genotypes, respectively (P for trend < 0.01). Four common haplotypes for the IGFBP3 gene were identified. Compared with the haplotype containing only the wild-type allele in the five loci, the haplotype with the variant allele in all sites was associated with an elevated risk of breast cancer (OR 1.4, 95% CI 1.0-1.9), particularly among younger women (OR 2.3, 95% CI 1.3-3.9). With the exception of C3804G, in which no homozygote was identified, the level of circulating IGFBP-3 was reduced in a dose-response manner with an increasing number of variant alleles in each of the other four polymorphic sites (P for trend < 0.05). These results indicated that IGFBP3 polymorphisms may be associated with the level of blood IGFBP-3 protein and an increased risk of breast cancer.

Adult↗

[Measurement of intracellular pH in long-chain dicarboxylic acid-producing yeast Candida tropicalis and its growth activity].

Intracellular pH (pHi) has an important influence on the metabolic activity of cells or cellular processes. The intracellular pH (pHi) of long-chain alpha,omega-dicarboxylic acid-producing Candida tropicalis was determined by fluorescence technique using a pH-sensitive fluorescent probe 5(6)-carboxyfluorescein diacetate. Optimal loading conditions of the fluorescent probe into the cells were experimentally determined. Effects of extracellular pH and carbon sources for growth on pHi in the cell grown in a flask were studied; the results indicated that extracellular pH has a slight influence on pHi, whereas carbon sources such as sucrose, glucose, acetic acid, and n-tridecane showed moderate influences. Further work on the relationship between the cell growth activity and pHi was carried out in a 5 L bioreactor. The time course of specific rates of the cell growth, glucose consumption, CO2 production, and pH gradients across cell plasma membrane were plotted, where the cell growth was improved by the higher pHi at 8 - 12 h. The measured pHi values were varied from 5.72 to 6.15 at medium pH 6.0 in which glucose and sodium acetate were used together as carbon source. The investigation of pHi can be helpful for understanding its effects on the kinetics of the metabolic steps involved in the synthesis rate of alpha,omega-dicarboxylic acid and alpha,omega-dicarboxylic acid transport across plasma membranes.

Candida tropicalis↗

[Clinical evaluation of extensively damaged pulpless anterior teeth restored with direct and indirect cast dowel-core crowns].

OBJECTIVE: To compare the clinical effects of the restoration of residual crowns and roots with direct and indirect cast dowel-core crowns. METHODS: The direct and indirect techniques were applied to fabricate cast dowel-core in 119 teeth of 91 patients. The direct dowel-cores were made by fabricating wax patterns in the prepared teeth in the patients' mouth; and the indirect dowel-cores were fabricated with wax patterns on casts poured by injecting agar impression material into the canal. Then the completed wax patterns were invested. After finishing the dowel-cores, they were cemented in the teeth. The metalceramic crowns were made to restore these teeth. RESULTS: Of the 119 teeth, 71 succeeded and 5 failed in 76 dowel-cores made by the direct method; and only 1 tooth failed among the 43 dowel-cores made by the indirect method. CONCLUSION: The indirect method using agar impression material can be manipulated easily and conveniently with accurate impressions. The dowel-core fits the root canal and the margin has good adaption. The retention is good and this method is practicable.

Adult↗

Near-infrared optical imaging of epidermal growth factor receptor in breast cancer xenografts.

The specificity of a novel epidermal growth factor (EGF)-Cy5.5 fluorescent optical probe in the detection of EGF receptor (EGFr) was assessed using continuous-wave fluorescence imaging accomplished via an intensified charge-coupled device (CCD) camera. Human mammary MDA-MB-468 (EGFr+) and MDA-MB-435 (EGFr-) cancer cells were incubated with Cy5.5, EGF-Cy5.5, or the anti-EGFr monoclonal antibody C225 or EGF followed by EGF-Cy5.5 and examined under a fluorescence microscope. In vivo imaging was performed on mice with s.c. MDA-MB-468 and MDA-MB-435 tumors. Images were obtained every 6 s for 20 min after i.v. injection of each agent and every 24 h after injection for up to 192 h. Additionally, mice with MDA-MB-468 tumors were injected i.v. with C225 24 h before injection of EGF-Cy5.5. EGF-Cy5.5, but not Cy5.5 or indocyanine green dye (ICG), bound to MDA-MB-468 cells. Binding of EGF-Cy5.5 was blocked by C225 and by EGF. In contrast, binding of EGF-Cy5.5 to MDA-MB-435 cells was not observed. Monitoring of the time-fluorescence intensity in mice confirmed that ICG and Cy5.5 had no favorable binding to tumor regardless of EGFr expression level. In contrast, EGF-Cy5.5 accumulated only in MDA-MB-468 tumors. Moreover, tumor uptake of EGF-Cy5.5 was blocked by C225. ICG and Cy5.5 fluorescence was completely absent from the tumor site, regardless of EGFr expression level, 24 h after injection. Little EGF-Cy5.5 fluorescence was detected in MDA-MB-435 tumors 24 h after injection. In MDA-MB-468 tumors, our data suggest that EGF-Cy5.5 may be used as a specific NIR contrast agent for noninvasive imaging of EGFr expression and monitoring of responses to molecularly targeted therapy.

Adenocarcinoma↗

Fouling and natural organic matter removal in adsorbent/membrane systems for drinking water treatment.

Adsorbent particles added to ultrafiltration (UF) systems treating drinking water can remove natural organic matter (NOM) and some other contaminants from the water, but their effect on membrane fouling is inconsistent-in some cases, fouling is reduced, and in others, it is exacerbated. This research investigated the behavior of UF systems to which powdered activated carbon (PAC), heated iron oxide particles (HIOPs), or (nonadsorbent) SiO2 particles were added. On a mass basis, the PAC removed the most NOM from solution, the HIOPs removed less, and the SiO2 removed essentially none. However, in the case of both PAC and SiO2, increasing the dose of solids led to a steady increase in fouling, whereas the opposite trend applied when HIOPs were added. In the absence of NOM, none of the solids fouled the membrane significantly. Thus, even though NOM is a causative agent for fouling, removing it from solution does not necessarily reduce fouling; the mechanism of removal can be just as important as the absolute amount removed, if the removal occurs in a cake layer near the membrane surface. Scanning electron microscopy images of the cake layers formed in the three systems suggest that the NOM binds PAC or SiO2 particles to one another and to the membrane surface, so that the particles become part of the foulant in the system. By contrast, the NOM appears to bind HIOPs to one another but not to the membrane. This process leaves enough pore space in the cake layer for water to reach the membrane with minimal resistance, and it reduces the tendency for either the NOM or the HIOPs to foul the membrane surface.

Adsorption↗

Poly(L-glutamic acid)-paclitaxel conjugate is a potent enhancer of tumor radiocurability.

PURPOSE: Conjugating drugs with polymeric carriers is one way to improve selective delivery to tumors. Poly (L-glutamic acid)-paclitaxel (PG-TXL) is one such conjugate. Compared with paclitaxel, its uptake, tumor retention, and antitumor efficacy are increased. Initial studies showed that PG-TXL given 24 h before or after radiotherapy enhanced tumor growth delay significantly more than paclitaxel. To determine if PG-TXL-induced enhancement is obtained in a more clinically relevant setting, we investigated PG-TXL effects on tumor cure. METHODS AND MATERIALS: Mice bearing 7-mm-diameter ovarian carcinomas were treated with PG-TXL at an equivalent paclitaxel dose of 80 mg/kg, single dose or 5 daily fractions of radiation or both PG-TXL and radiation. Treatment endpoint was TCD(50) (radiation dose yielding tumor control in 50% of mice). Acute radioresponse of jejunum, skin, and hair was determined for all treatments. RESULTS: PG-TXL dramatically improved tumor radioresponse, reducing TCD(50) of single-dose irradiation from 53.9 (52.2-55.5) Gy to 7.5 (4.5-10.7) Gy, an enhancement factor (EF) of 7.2. The drug improved the efficacy of fractionated irradiation even more, reducing the TCD(50) of 66.6 (62.8-90.4) Gy total fractionated dose to only 7.9 (4.3-11.5) Gy, for an EF of 8.4. PG-TXL did not affect normal tissue radioresponse resulting from either single or fractionated irradiation. CONCLUSION: PG-TXL dramatically potentiated tumor radiocurability after single-dose or fractionated irradiation without affecting acute normal tissue injury. To our knowledge, PG-TXL increased the therapeutic ratio of radiotherapy more than that previously reported for other taxanes, thus, PG-TXL has a high potential to improve clinical radiotherapy.

Adenocarcinoma↗

Paclitaxel induces inactivation of p70 S6 kinase and phosphorylation of Thr421 and Ser424 via multiple signaling pathways in mitosis.

The 70 kDa ribosomal S6 kinase (p70S6K) is important for cell growth and survival. Activation of p70S6K requires sequential phosphorylation of multiple serine and threonine sites often triggered by growth factors and hormones. Here, we report that paclitaxel, a microtubule-damaging agent, induces phosphorylation of p70S6K at threonine 421 and serine 424 (T421/S424) in a concentration- and time-dependent manner in multiple breast and ovarian cancer cell lines demonstrated by a T421/S424 phospho-p70S6K antibody. Phosphoamino-acid analysis and Western blot analysis by serine-/threonine-specific antibodies further confirms that both serine and threonine residues are phosphorylated in p70S6K following treatment with paclitaxel. Paclitaxel-induced p70S6K(T421/S424) phosphorylation requires both de novo RNA and protein synthesis via multiple signaling pathways including ERK1/2 MAP kinase, JNK, PKC, Ca(++), PI3K, and mammalian target of rapamycin (mTOR). Despite phosphorylation of p70S6K(T421/S424), paclitaxel inactivates this kinase in a concentration- and time-dependent manner as illustrated by in vitro kinase assay. Inhibitors of mTOR, PI3K, and Ca(++) impair p70S6K activity, whereas inhibitors of JNK and PKC stimulate p70S6K activity. Inhibition of PKC and JNK prevents paclitaxel-induced p70S6K inactivation. Moreover, the paclitaxel-induced phosphorylation and low activity of p70S6K mainly occurs during mitosis. In summary, paclitaxel is able to induce p70S6K(T421/S424) phosphorylation and decrease its activity in mitotic cells via multiple signaling pathways. Our data suggest that paclitaxel-induced p70S6K(T421/S424) phosphorylation and kinase inactivation are differentially regulated. Our data also indicate that paclitaxel may exert its antitumor effect, at least in part, via inhibition of p70S6K.

Antineoplastic Agents, Phytogenic↗

Intracellular pH and metabolic activity of long-chain dicarylic acid-producing yeast Candida tropicalis.

The intracellular pH (pH(i) of alpha-omega-dicarylic acid producing Candida tropicalis was determined by a fluorescence technique using the pH-sensitive fluorescent probe 5(6)-carboxyfluorescein diacetate. Fermentations with n-tridecane substrate to produce alpha,omega-tridecanedioic acid were carried out in a 5-l bioreactor in which growth and production were separated. During the growth phase, the measured pH(i) values were varied from 5.65 to 6.15 in all the experiments performed under different constant pH-operating conditions. The specific rates of growth, sucrose consumption, CO2 production, and O2 consumption were correlated with pH(i). Cytochrome P450 monooxygenase (P450), which catalyzes n-alkane hydroxylation, was only slightly expressed during the growth phase. During the first 6 h of the production phase, P450 activity was induced rapidly accompanying higher pH(i). A much higher level of P450 activity was observed at pH(i) of 6.55+/-0.15 for all the fermentations, with maximum productivity (1.919 g/l/h) occurring when using an optimal pH-control strategy. However, P450 activity, tridecanedioic acid productivity, and pH(i) decreased progressively during the latter part of the production phase, as a consequence of the metabolic activity changes of the cells. Even though culture pH has only a slight influence on pH(i), the metabolic activity of C. tropicalis is sensitive to the variations in pH(i). The measured pH(i) varied from 6.1 to 6.7 during the production phase for all the fermentations. Thus, both tridecanedioic acid productivity and P450 activity are correlated with pH(i) or pH gradients across the cell membrane.

Journal Article↗

Targeting doxorubicin to epidermal growth factor receptors by site-specific conjugation of C225 to poly(L-glutamic acid) through a polyethylene glycol spacer.

PURPOSE: Targeted delivery of chemotherapeutic agents through antibody-polymer conjugates has met with limited success. One of the limiting factors is the loss of antibody's binding affinity upon conjugation with polymeric carriers because of lack of control over the number and site of attachment. This study aims to synthesize monovalent polymeric immunoconjugates through site-specific conjugation and to evaluate the in vitro binding activities of the resulting construct. METHODS: Antibody C225 against epidermal growth factor receptors was coupled to the terminus of a doxorubicin-bound block copolymer, poly(L-glutamic acid)-co-polyethylene glycol (PG-PEG). Western blot analysis, confocal fluorescent microscopy, and cytotoxicity assay were performed to confirm the specific binding of C225-PEG-PG-Dox to EGFR. RESULTS: C225 was conjugated to PEG-PG-doxorubicin conjugates by reacting sulfhydryl group introduced to C225 with vinylsulfone group introduced at the terminus of PEG-PG block copolymer. Polymeric immunoconjugate C225-PEG-PG-Dox, but not control (i.e., conjugate without antibody), selectively bound to human vulvar squamous carcinoma A431 cells that overexpress epidermal growth factor receptors. Receptor-mediated uptake of C225-PEG-PG-Dox occurred rapidly (within 5 min), whereas nonspecific uptake of PEG-PG-Dox required an extended period of time (24 h) to internalize. Binding of C225-PEG-PG-Dox to A431 cells could be blocked by pretreatment with C225 antibody. C225-PEG-PG-Dox was more potent than free doxrubicin in inhibiting the growth of A431 cells after a 6-h exposure period. CONCLUSION: Site-specific conjugation of a monoclonal antibody to the terminus of a polymeric carrier enhances receptor-mediated delivery of anticancer agents.

Antibodies, Monoclonal↗

A structured kinetic model for suspension cultures of Taxus chinensis var. mairei induced by an oligosaccharide from Fusarium oxysporum.

A structured kinetic model was established to describe the process of Taxol formation in suspension cultures of Taxus chinesis var. mairei induced by an oligosaccharide from Fusarium oxysporum. In this model, the role of intracellular starch as a storage carbon source had to be taken into account. Substrate uptake, culture growth, cell respiration, and secondary metabolites, predicted by the model, agreed with those obtained experimentally. The effective factors of oligosaccharide elicitation, eta(e,j), defined as the ratio of the parameter values in the system with oligosaccharide to those in control, reflected the effects of the oligosaccharide on cell growth and Taxol production.

Bioreactors↗

Improved radiolabeling of PEGylated protein: PEGylated annexin V for noninvasive imaging of tumor apoptosis.

We have developed a one-step procedure to introduce both polyethylene glycol (PEG) and the metal chelator diethylenetriaminepentaacetic acid (DTPA) to proteins through a heterofunctional PEG precursor. The PEG precursor contains DTPA at one end and an amine-reactive isothiocyanate (SCN-) functional group at the other end. It was obtained as lyophilized powder and could be stored at 4 degrees C for several months. Protein conjugation was achieved by simply mixing the proteins and the PEG precursor SCN-PEG-DTPA in an aqueous solution. As exemplified by the PEGylation and radiolabeling of annexin V, the resulting conjugate 111In-DTPA-PEG-annexin V showed selective binding to apoptotic cells in vitro and increased blood half-life in vivo. The PEGylated, radiolabeled annexin V may be useful in the noninvasive imaging of apoptosis.

Animals↗

Numerical characterization and similarity analysis of DNA sequences based on 2-D graphical representation of the characteristic sequences.

Based on the classifications of the four nucleic acid bases, He and Wang reduced a DNA sequence to three binary sequences, which are called the characteristic sequences (J. Chem. Inf. Comput. Sci. 42 (2002) 1080). In this paper, we associate each characteristic sequence with a (b)L / (b)L matrix by giving a 2-D 'two horizontal lines' graphical representation, and thus obtain a 3-component vector with entries being the sums of the maximal and minimal eigenvalues of the (b)L / (b)L matrices. The introduced vector results in more simple characterizations and comparisons among the coding sequences of exon 1 of beta-globin gene of eleven different species.

Animals↗

[Influence of electro-acupuncture of Neiguan on plasmic concentrations of NO and TNFalpha in endotoxin shock rats].

OBJECTIVE: To observe the effect of electro-acupuncture of Neiguan (PC 6) on mean systemic arterial blood pressure and plasmic concentrations of NO and TNFalpha in endotoxin shock rats. METHODS: The model of endotoxin shock was induced by lipopolysaccharide (1.5 mg/kg i.v.) and D-galactosamine (100 mg/kg i.p.). Aminoguanidine (100 mg/kg i.p.) and electro-acupuncture of bilateral Neiguan (PC 6) were administered. A catheter was inserted into the right subclavian artery to record the change of blood pressure and the blood was abstracted out and centrifuged to determine the NO and TNFalpha concentrations. RESULTS: Electro-acupuncture of Neiguan (PC 6) retrieved the blood pressure and reduced the plasmic NO and TNFalpha concentrations. CONCLUSION: Electro-acupuncture of Neiguan (PC 6) expresses an anti-endotoxin shock effect by repressing the plasmic NO and TNFalpha concentrations smoothly and retrieving the blood pressure stably.

Acupuncture Points↗

Correlation between expression of human telomerase subunits and telomerase activity in esophageal squamous cell carcinoma.

AIM: To investigate telomerase activity and hTERT, TP-1 expression and their relationships in esophageal squamous cell carcinoma (ESCC). METHODS: Telomerase activity was measured in 60 ESCC tissues using telomeric repeat amplification protocol (TRAP) assay by silver staining. In situ hybridization was used for detecting hTERT and TP-1mRNA. RESULTS: The telomerase activity was detected in 83.3% of ESCC tissues. The difference of telomerase activity was significant between well and poorly cancer differentiated lesions (P<0.05). The positive rate of telomerase activity was higher in patients with lymphatic metastasis than in patients without lymphatic metastasis. In cancer tissues hTERT mRNA expression was 75% and TP-1 mRNA expression was 71.7%. The expression of hTERT, TP-1 mRNA in well and poorly differentiated carcinoma was not significant. The expression of hTERT mRNA was correlated with telomerase activity, but TP-1 mRNA expression was not correlated with it. CONCLUSION: Telomerase activity and hTERT, TP-1 mRNA expression are up-regulated in ESCC. Telomerase activity in ESCC is correlated with lymphatic metastasis and cancer differentiation. Telomerase activity may be used as a prognostic marker in ESCC. hTERT mRNA expression is correlated with telomerase activity. Enhanced hTERT mRNA expression may initially comprehend the telomerase activity level, but it is less sensitive than TRAP assay.

Adult↗

Clinical effect of removable partial denture prepared by Saddle-Lock hidden-clasp.

OBJECTIVE: To study the method for preparing removable partial denture using Saddle-Lock hidden-clasp and evaluate its clinical effect. METHOD: Casting process was adopted for the preparation of the clasp, which was fixed at the points on the mesial and distal surfaces of the abutment tooth. The clinical records of 305 patients treated with such removable partial dentures were reviewed. RESULTS: Within a follow-up period of 6 years, 295 of the 305 patients retained good abutment condition and were satisfied with the denture that was capable of easy wearing and removing. CONCLUSIONS: Removable partial denture made by Saddle-lock hidden-clasp exhibits good performance in fixation and stability. As an innovation of traditional design of partial denture clasp, it is simple to prepare and well received by the patients with good clinical effect.

Adult↗

Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters.

A detailed SAR study directed toward the optimization of pharmacokinetic parameters for analogues of L-791,943 is reported. The introduction of a soft metabolic site on this structure permitted the identification of L-826,141 as a potent phosphodiesterase type 4 (PDE4) inhibitor that is well absorbed and that presents a shorter half-life than L-791,943 in a variety of animal species. The efficacy of L-826,141 is also demonstrated in different in vivo models.

3',5'-Cyclic-AMP Phosphodiesterases↗

Poly(L-glutamic acid)--anticancer drug conjugates.

Chemotherapy has had limited success in the treatment of cancer over the years, due, in part, to the untoward toxicity of the therapeutic agent to normal cells. The design of tailor-made polymer conjugates provides a synthetic approach that can overcome some of the problems. Several synthetic polymer-based anticancer drug conjugates have entered clinical studies. This report reviews the chemistry, physicochemical properties, and therapeutic applications in cancer therapy of polymeric chemotherapeutic agents based on poly(L-glutamic acid). Targeted delivery of anticancer agents using poly(L-glutamic acid) as the drug carrier is also discussed with emphasis on the design of innovative polymeric constructs.

Anthracyclines↗