Utilisation of Nanoparticle Technology in Cancer Chemoresistance

Table 1

Overview of a selection of cytotoxic drugs commonly used in chemotherapy.

Cytotoxic drug	Mechanism of action	Major adverse effects	References
Cisplatin	Inter/intrastrand cross-link formation on nucleophilic N7 sites of adjacent adenine and guanine bases, leading to apoptosis.	Dose-dependent ototoxicity nephrotoxicity, neurotoxicity, and myelosuppression.	[3–9]
Carboplatin	Inter/intrastrand cross-link formation on nucleophilic N7 sites of adjacent adenine and guanine bases, leading to apoptosis.	Dose-dependent myelosuppression.	[3, 4]
Cyclophosphamide	Oxazaphosphorine DNA-alkylating pro-drug, activated by liver P450 cytochrome-induced 4-hydroxylation., thus forming DNA cross-linking phosphoramide mustard.	Neurotoxicity and nephrotoxicity due to chloroacetaldehyde formation by P450 cytochrome-induced oxidation.	[10]
Doxorubicin	Anthracycline-glucuronide conjugate prodrug activated by tumour β-glucuronidase, whereby the drug/DNA adduct possibly induces apoptosis by topoisomerase 2 inhibition or by a caspase cascade.	Dose-dependent cardiotoxicity, hepatotoxicity, and myelosuppression.	[11–15]
Etoposide	Topoisomerase II inhibitor, by raising the stability of the enzyme/DNA cleavage complex, ultimately leading to DNA strand breaks and apoptosis.	Possible secondary leukaemia due to chromosomal translocations induced by etoposide strand break activity, myelosuppression.	[16–22]
Ifosfamide (in severe NB cases)	Oxazaphosphorine DNA-alkylating prodrug, activated by liver P450 cytochrome-induced 4-hydroxylation, thus forming DNA cross-linking phosphoramide mustard.	Marked neurotoxicity and nephrotoxicity due to increased chloroacetaldehyde formation by P450 cytochrome-induced oxidation.	[10]