Hypocrellin derivative with improvements of red absorption and active oxygen species generation

A novel diamino-substituted hypocrellin derived from hypocrellin B (HB) was synthesized by a mild method. The red absorption of the resulting product was significantly enhanced relative to the parent hypocrellins and any other hypocrellin derivatives, and the active oxygen species generating abilities were enhanced distinctly, which will remarkably improve its photodynamic therapy effectiveness.     

A novel method for the preparation of amino-substituted hypocrellin B.

A series of amino-substituted hypocrellins derived from hypocrellin B (HB) were synthesized by a novel mild method, in which the peri-hydroxylated perylenequinone structure of hypocrellin was preserved by the reaction of HB with an amine. The red absorption of the resulting products was significantly enhanced relative to the parent hypocrellins, which will significantly improve its photodynamic therapy effectiveness.     

Synergistic anti-tumor effects of combination of photodynamic therapy and arsenic compound in cervical cancer cells: in vivo and in vitro studies

The effects of As(4)O(6) as adjuvant on photodynamic therapy (PDT) were studied. As(4)O(6) is considered to have anticancer activity via several biological actions, such as free radical production and inhibition of VEGF expression. PDT or As(4)O(6) significantly inhibited TC-1 cell proliferation in a dose-dependent manner (P<0.05) by MTT assay. The anti-proliferative effect of the combination treatment was significantly higher than in TC-1 cells treated with either photodynamic therapy or As(4)O(6) alone (62.4 and 52.5% decrease compared to vehicle-only treated TC-1 cells, respectively, P<0.05). In addition, cell proliferation in combination of photodynamic therapy and As(4)O(6) treatment significantly decreased by 77.4% (P<0.05). Cell survival pathway (Naip1, Tert and Aip1) and p53-dependent pathway (Bax, p21(Cip1), Fas, Gadd45, IGFBP-3 and Mdm-2) were markedly increased by combination treatment of photodynamic therapy and As(4)O(6). In addition, the immune response in the NEAT pathway (Ly-12, CD178 and IL-2) was also modulated after combination treatment, suggesting improved antitumor effects by controlling unwanted growth-stimulatory pathways. The combination effect apparently reflected concordance with in vitro data, in restricting tumor growth in vivo and in relation to some common signaling pathways to those observed in vitro. These findings suggest the benefit of combinatory treatment with photodynamic therapy and As(4)O(6) for inhibition of cervical cancer cell growth.     

ESR evidence of the photogeneration of free radicals (GDHB*-, O2*-) and singlet oxygen ((1)O2) by 15-deacetyl-13-glycine-substituted hypocrellin B

15-Deacetyl-13-glycine-substituted hypocrellin B (GDHB) is a new type of hypocrellin derivative with an enhanced red absorption longer than 600 nm and water solubility. Visible light (> 470 nm) irradiation of an anaerobic aqueous solution of GDHB, the formation of GDHB*- was detected by an ESR method in the absence or presence of electron donor. When exposed to oxygen, superoxide anion radical and singlet oxygen were formed. The superoxide anion radical was generated by GDHB*- via electron transfer to oxygen and this process was significantly enhanced by the presence of electron donors. Singlet oxygen ((1)O2) was also formed in the photosensitization of GDHB in aerobic solution and 1,4-diazabicyclo [2,2,2] octane (DABCO), sodium azide (NaN3) and histidine inhibited the generation of (1)O2. A 9,10-diphenyl antracene (DPA)-bleaching method was used to determine the quantum yield of (1)O2 generated from GDHB photosensitization. The (1)O2 quantum yield was estimated to be 0.65. With the depletion of oxygen, the accumulation of GDHB*- would replace that of (1)O2. Evidence accumulated that the photodynamic action of GDHB may proceed via both type I and type II mechanisms and that a type II mechanism will be transformed into a type I mechanism as oxygen gets depleted.     

Effect of structural modifications on photosensitizing activities of hypocrellin dyes: EPR and spectrophotometric studies.

Mono-substituted hypocrellin B (MHB) and di-substituted hypocrellin B (DHB) by mercaptoacetic acid are new photosensitizers synthesized to improve the red absorption and water solubility of the parent hypocrellin B (HB). The photochemistries (Type I and/or Type II) of MHB and DHB have been studied in homogeneous solutions using electron paramagnetic resonance (EPR) and spectrophotometric methods. In anaerobic homogeneous DMSO solution, DHB*- (or MHB*-) was predominantly photoproduced via self-electron transfer between the excited- and ground-state species. The presence of an electron donor significantly promotes the formation of the reduced form of DHB (or MHB). As compared with hypocrellin B, the efficiencies of DHB*- and MHB*- generation was enhanced obviously. When oxygen-saturated solutions of DHB (or MHB) were illuminated with 532 nm light, singlet oxygen (1O2), superoxide anion radical (O2*-), hydroxyl radical (*OH) and hydrogen peroxide (H2O2) were formed. DHB and MHB generate 1O2 with quantum yields of 0.18 and 0.22, respectively, which are much lower than that of HB (0.76) in chloroform. The superoxide anion radical was significantly enhanced by the presence of electron donors. The rate of O2*- production was also dependent on the concentration of DHB or MHB. Moreover, O2*- upon disproportionation can generate H2O2 and ultimately the highly reactive *OH via the Fenton reaction and other pathway with the involvement of DHB*- (or MHB*-). As in the case of DHB*- (or MHB*-), the efficiencies of O2*- and *OH generation by DHB and MHB were also enhanced obviously, consistent with the fact that DHB*- (or MHB*-) acts as the precursor of O2* and thus *OH. These findings suggest that the photodynamic actions of DHB and MHB may proceed via enhanced Type I mechanism and reduced Type II mechanism as compared with that of HB.     

Time course and quantitative analysis of the adaptive responses to 85% oxygen in the rat lung and heart

The phenomenon of oxygen tolerance (resistance to 100% O(2) in rats previously exposed to 85% O(2)) constitutes one of the few models of adaptive responses to oxidative stress in mammals. In vitro studies suggest that reactive oxygen species mediate this response. To test this hypothesis in vivo, we followed the time course of oxidative stress, enzyme induction, and edema in the lung, heart and liver of rats exposed to 85% O(2) for 1 to 5 days. Interestingly, not only the lung, but also the heart of rats exposed to 85% O(2) showed increases in the production of O(*-)(2) (aconitase inactivation) early during the exposure. Increases in O(*-)(2) were associated to oxidative stress (increased in situ chemiluminescence) and transient edema in both tissues. Both the lung and heart displayed induction of superoxide dismutase and reversion of the oxidative stress and damage. The adaptive response in the heart was faster and more efficient, suggesting that this tissue is at a more critical risk when exposed to elevated O(2) concentrations.     

Evidence that hydroxyl radicals mediate auxin-induced extension growth

Reactive oxygen intermediates, i.e. the superoxide radical (O*-)(2), hydrogen peroxide (H2O2) and the hydroxyl radical (*OH), are generally regarded as harmful products of oxygenic metabolism causing cell damage in plants, animals and microorganisms. However, oxygen radical chemistry may also play a useful role in polymer breakdown leading to wall loosening during extension growth of plant cells controlled by the phytohormone auxin. Backbone cleavage of cell wall polysaccharides can be accomplished in vitro by (*OH) produced from H2O2 in a Fenton reaction or in a reaction catalyzed by peroxidase supplied with O2 and NADH. Here, we show that coleoptile growth of maize seedlings is accompanied by the release of reactive oxygen intermediates in the cell wall. Auxin promotes release of (O*-)(2) and subsequent generation of (*OH)when inducing elongation growth. Experimental generation of (*OH) in the wall causes an increase in wall extensibility in vitro and replaces auxin in inducing growth. Auxin-induced growth can be inhibited by scavengers of (O*-)(2), H2O2 or (*OH), or inhibitors interfering with the formation of these molecules in the cell wall. These results provide the experimental background for a novel hypothesis on the mechanism of plant cell growth in which (*OH), produced from (O*-)(2) and H2O2 by cell wall peroxidase, acts as a wall-loosening agent.     

Photodynamic effects of two hydroxyanthraquinones

The aim of this work was to investigate the photodynamic action of electron-rich anthraquinones, viz., cynodontin (CYN) and cynodontin-5,8-dimethylether (CYNM). Both optical and EPR methods are used to detect the generation of singlet oxygen. Based on RNO bleaching, relative to rose bengal (RB), singlet oxygen generating efficiencies of CYN and CYNM are derived to be 0.055 and 0.254, respectively. The formation of superoxide anion via electron transfer to O2 was monitored by optical spectroscopy, using SOD-inhibitable cytochrome c reduction assay. The production of O2-* is enhanced in the presence of electron donors such as EDTA and NADH. Photolysis of CYN and CYNM in DMSO, in the presence of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), generates a multi-line EPR spectrum, characteristic of spin adduct mixture of O2-* and *OH. Both optical and ESR measurements indicate that O2-* (Type I) and 1O2 (Type II) paths are involved in CYN and CYNM photodynamic action.     

Evidence for the involvement of singlet oxygen in the photodestruction by chloroaluminum phthalocyanine tetrasulfonate

In recent years, choloroaluminum phthalocyanine tetrasulfonate (A1PCTS) has been shown to be a promising photosensitizer for the photodynamic therapy (PDT) of cancer. Although its mechanism of photodynamic action is not well defined, A1PCTS is going to be under clinical trials of PDT. In this study, in vitro addition of A1PCTS to a suspension of rat epidermal microsomes followed by irradiation with red light (approximately 675 nm) resulted in significant destruction of cytochrome P-450 and associated monooxygenase activities. The photodestructive effect was dependent on both the dose of A1PCTS and the duration of light exposure. Studies using various quenchers of reactive oxygen species showed that only scavengers of singlet oxygen such as histidine, 2,5-dimethylfuran, beta-carotene and sodium azide afforded substantial protection against photodestruction. Our data indicate the direct involvement of singlet oxygen in the A1PCTS-mediated photodestructive process.     

Binding of hypocrellin B to human serum albumin and photo-induced interactions

Molecular binding of hypocrellins to human serum albumin (HSA) needs to be further clarified considering the phototherapeutic potentials of hypocrellins to vascular diseases. In the current work, it was estimated that the binding constant of hypocrellin B (HB) to HSA was 2.28 x 10(4) M(-1). Furthermore, based on the fluorescence responses for both HB and the tryptophan of HSA, it was suggested that the binding of HB to HSA should be more specific rather than distributed randomly on the surface of HSA, which was also confirmed by photobleaching of the tryptophan via photosensitization of HB. Besides, it was found that both of the photo-bleaching of the tryptophan and the photo-oxidation of HB were principally oxygen-dependent, suggesting reactive oxygen species generated via the photosensitization of HB, instead of the free radicals of the photosensitizer (HB*-), play the most important role in photodynamic processes.     

The metabolism of sulindac enhances its scavenging activity against reactive oxygen and nitrogen species

Sulindac is a sulfoxide prodrug that, in vivo, is converted to the metabolites sulindac sulfide and sulindac sulfone. It is therapeutically used as an anti-inflammatory and analgesic in the symptomatic treatment of acute and chronic rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. In addition to its anti-inflammatory properties, sulindac and its metabolites have been shown to have an important role in the prevention of colonic carcinogenesis. Although the inhibition of prostaglandin synthesis constitutes the primary mechanism of action of sulindac, it is well known that reactive oxygen species (ROS) and reactive nitrogen species (RNS) are implicated in the pathophysiology of inflammation and cancer. Thus, the aim of this study was to evaluate the scavenging activity of sulindac and its sulfone and sulfide metabolites for an array of ROS (HO*, O2(*-), and HOCl) and RNS (*NO and ONOO-) using in vitro systems. The results we obtained demonstrate that the metabolism of sulindac increases its scavenging activity for all RNS and ROS studied, notably with regard to the scavenging of HOCl. These effects may strongly contribute to the anti-inflammatory and anticarcinogenic efficacy that has been shown for sulindac.     

Photodynamic anticancer activities of water-soluble C(60) derivatives and their biological consequences in a HeLa cell line

Photodynamic therapy is an emerging, externally activatable, treatment modality for various diseases, especially for cancer therapy. The photodynamic activities of tumor targeting water-soluble C(60) derivatives (WSFD) were evaluated on HeLa cells. To overcome the poor solubility, biocompatibility and selectivity of C(60), we modified C(60) with l-phenylalanine, folic acid and l-arginine. Consistent with their photodynamic abilities, WSFD generated the reactive oxygen species after irradiation both in water and in vitro. No dark cytotoxicity was observed using 5μg/mL WSFD during long incubation time. Furthermore, the uptake of WSFD into HeLa cells was much more than normal cells, which indicated the WSFD had selectivity to tumor cells. Investigation of the possible photodynamic activities of WSFD demonstrated that they expressed photokilling activities by raising the level of (1)O(2)/O(2)(-) under visible light irradiation. In parallel, following exposure of cells to WSFD and irradiation, a marked decrease in mitochondrial membrane potential, cell viability, activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), as well as increased malondialdehyde (MDA) production were observed. Moreover, WSFD caused significant elevation in caspase-3 activity, and induced apoptotic death. Experiments demonstrated that both chemical properties, such as the chemical structure of adduct and addend numbers, and physical properties, such as degree of aggregation, influenced the ROS-generation abilities, cellular uptake and photodynamic activities of WSFD. The results suggest that WSFD have the potential application in cancer cell inactivation by photodynamic therapy.     

Oxygen consumption and diffusion effects in photodynamic therapy

Effects of oxygen consumption in photodynamic therapy (PDT) are considered theoretically and experimentally. A mathematical model of the Type II mechanism of photooxidation is used to compute estimates of the rate of therapy-dependent in vivo oxygen depletion resulting from reactions of singlet oxygen (1O2) with intracellular substrate. Calculations indicate that PDT carried out at incident light intensities of 50 mW/cm2 may consume 3O2 at rates as high as 6-9 microM s-1. An approximate model of oxygen diffusion shows that these consumption rates are large enough to decrease the radius of oxygenated cells around an isolated capillary. Thus, during photoirradiation, cells sufficiently remote from the capillary wall may reside at oxygen tensions that are low enough to preclude or minimize 1O2-mediated damage. This effect is more pronounced at higher power densities and accounts for an enhanced therapeutic response in tumors treated with 360 J/cm2 delivered at 50 mW/cm2 compared to the same light dose delivered at 200 mW/cm2. The analysis further suggests that the oxygen depletion could be partially overcome by fractionating the light delivery. In a transplanted mammary tumor model, a regimen of 30-s exposures followed by 30-s dark periods produced significantly longer delays in tumor growth when compared to the continuous delivery of the same total fluence.     

Photogeneration of free radicals (*OH and HB*-) and singlet oxygen (1O2) by hypocrellin B in TX-100 micelles microsurroundings

To solve the problems faced in clinical use of hypocrellins, a water-soluble preparation of Hypocrellin B (HB), HB-Triton X-100 (TX-100) micelles, was prepared. To evaluate the photodynamic activity, the free radicals (^•OH and HB^•¯) and singlet oxygen (

1

O

2

) generated via photosensitization of the preparation in aqueous solution were detected by using electron paramagnetic resonance (EPR) and spectrophotometric methods. It was observed that

1

O

2

was formed with a quantum yield of 0.72, similar to that for HB in organic solvents, further, hydroxyl radicals (

•

OH) could also be efficiently produced by the new preparation, which have never before been detected following HB photoactivities. In addition, the semiquinone anion radicals (HB^•-) could also be generated via the self-electron transfer between an excited triplet state and a ground state molecule. The accumulation of HB^•- would replace that of

•

OH or

1

O

2

with the depletion of oxygen in the system. All these findings suggested that the HB-TX-100 micelles could play the photodynamic action through not only the type I mechanism by free radicals (^•OH, O₂^•- and HB^•-) but also the type II mechanism by singlet oxygen (

1

O

2

). It can be concluded further that the new preparation basically maintains the inherent photodynamic activity of HB, or even higher.     

Experimental study on photodynamic diagnosis of cancer mediated by chemiluminescence probe

A novel method of photodynamic diagnosis of cancer mediated by chemiluminescence probe is presented. The mechanism for photodynamic therapy involves singlet oxygen ((1)O(2)) generated by energy transfer from photosensitizers. (1)O(2) can react with 3,7-dihydro-6-[4-[2-(N'-(5-fluoresceinyl)thioureido)ethoxy]phenyl]-2-methylimidazo[1,2-a]pyrazin-3-one sodium salt (FCLA), which is a Cypridina luciferin analog and a specific chemiluminescence probe for detecting (1)O(2) and superoxide (O(2)(-)). The reaction of FCLA and (1)O(2) can give emission with peak wavelength at about 532 nm. In the present study, FCLA was chosen as an optical reporter of (1)O(2) produced from the photosensitization reaction of hematoporphyrin derivative in model solution and in nude mice with transplanted mammary cancer. Photosensitized chemiluminescence from the reaction of FCLA with (1)O(2) was detected by a highly sensitive Intensified Charge-Coupled Device detector. The chemiluminescence was markedly inhibited by the addition of 10 mmol/l sodium azide (NaN(3)) to the model solution and minor effects were observed at the addition of 10 micromol/l superoxide dismutase, 20 mmol/l mannitol and 100 microg/ml catalase, respectively, thus indicating that (1)O(2) generation from photosensitization reaction mainly results in light emission. Experiments in vivo with tumor-bearing mice showed a clear chemiluminescence image of tumor. The study suggests that this novel method may be applicable to the diagnosis of superficial tumors.     

Photodynamic inactivation of Escherichia coli by novel meso-substituted porphyrins by 4-(3-N,N,N-trimethylammoniumpropoxy)phenyl and 4-(trifluoromethyl)phenyl groups.

The photodynamic effect of novel cationic porphyrins, with different pattern of meso-substitution by 4-(3-N,N,N-trimethylammoniumpropoxy)phenyl (A) and 4-(trifluoromethyl)phenyl (B) groups, have been studied in both solution bearing photooxidizable substrates and in vitro on a typical Gram-negative bacterium Escherichia coli. In these sensitizers, the cationic groups are separated from the macrocycle ring by a propoxy spacer. Thus, the charges have a high mobility and a minimal influence on photophysical properties of the porphyrin. These compounds produce singlet molecular oxygen, O2(1Delta(g)), with quantum yields of approximately 0.41-0.53 in N,N-dimethylformamide. In methanol, the l-tryptophan photodecomposition increases with the number of cationic charges in the sensitizer. In vitro investigations show that cationic porphyrins are rapidly bound to E. coli cells in approximately 5 min. A higher binding was found for A3B3+ porphyrin, which is tightly bound to cells still after three washing steps. Photosensitized inactivation of E. coli cellular suspensions follows the order: A3B3+ > A44+> ABAB2+ > AB3+. Under these conditions, a negligible effect was found for 5,10,15,20-tetra(4-sulfonatophenyl)porphyrin (TPPS4(4-)) that characterizes an anionic sensitizer. Also, the results obtained for these new cationic porphyrins were compared with those of 5,10,15,20-tetra(4-N,N,N-trimethylammonium phenyl)porphyrin (TTAP4+), which is a standard active sensitizer established to eradicate E. coli. The photodynamic activity of TTAP4+ is quite similar to that produced by A4(4+). Studies in an anoxic condition indicate that oxygen is necessary for the mechanism of action of photodynamic inactivation of bacteria. The higher photodynamic activity of A3B3+ was confirmed by growth delay experiments. Photodynamic inactivation capacities of these sensitizers were also evaluated in E. coli cells immobilized on agar surfaces. Under these conditions, A3B3+ porphyrin retains a high activity to inactivate localized bacterial cells. Therefore, tricationic porphyrin A3B3+ is an interesting sensitizer with potential applications in photodynamic inactivation of bacteria in liquid suspensions or on surfaces.     

Using the singlet oxygen scavenging property of carotenoid in photodynamic molecular beacons to minimize photodamage to non-targeted cells.

We recently introduced the concept of photodynamic molecular beacons (PMB) for selective control of photodynamic therapy (PDT). The PMB consists of a peptide linker that is sequence specific to a cancer-associated protease. A photosensitizer (PS) and a singlet oxygen (1O2) quencher are conjugated to the opposite ends of this linker. Proximity of the PS and quencher can efficiently inhibit 1O2 generation. In the presence of a targeted protease, the substrate sequence is cleaved and the PS and quencher will separate so that the PS can be photo-activated. There are two ways to optimize the PMB selectivity to cancer cells. The first is to increase the protease specificity to targeted cells and the second is to minimize the phototoxicity of intact (uncleaved) PMBs in non-targeted (normal) cells. Carotenoids (CARs) are well known in nature for their role in quenching excited states of PS and in directly scavenging 1O2. The purpose of this study is to evaluate whether the CAR with dual quenching modes (PS excited states deactivation and 1O2 scavenging) can be used to minimize the photodamage of intact PMBs to non-targeted cells. Thus, we synthesized a beacon (PPC) with a caspase-3 cleavable peptide linking a PS and a CAR quencher. It was confirmed that CAR deactivates the PS excited states and also directly scavenges 1O2. Moreover, the in vitro PDT response showed that CAR completely shuts off the photodynamic effect in non-targeted HepG(2) cells, while PS without CAR (control) remains highly potent even at a much lower (30-fold) dose.     

Anti-oxidant and pro-oxidant behaviour of bucillamine.

Bucillamine (BUC) is used clinically for the treatment of rheumatoid arthritis. Some of the pharmacological action of BUC has been reported as being dependent on the production of reactive oxygen species (ROS). In this paper the reactivity of BUC with superoxide anion radical (O(2) (*-)) generated from potassium superoxide/18-crown-6 ether dissolved in DMSO, hydroxyl radical (HO(*)) produced in the Cu(2+)-H(2)O(2) reaction, peroxyl radical (ROO(*)) from 2,2'-azobis (2-amidino-propane) dichloride decomposition, and singlet oxygen ((1)O(2)) from a mixture of alkaline aqueous H(2)O(2) and acetonitrile, have been investigated. Chemiluminescence, fluorescence, electron paramagnetic resonance (EPR) spin-trapping techniques and the deoxyribose and oxygen radical absorbance capacity towards ROO(*) (ORAC(ROO)) assays were used to elucidate the anti- and pro-oxidative behaviours of BUC towards ROS. The results indicated that BUC efficiently inhibited chemiluminescence from the O(2) (*-)-generating system at relatively high concentrations (0.5-2 mmol/L); however, at lower concentrations (<0.5 mmol/L) the drug enhanced light emission. The behaviour of BUC was correlated with a capacity to decrease the chemiluminescence signal from the Cu(2+)-H(2)O(2) system; scavenging HO(*) was effective only at high concentrations (1-2 mmol/L) of the drug. Bucillamine also prevented deoxyribose degradation induced by HO(*) in a dose-dependent manner, reaching maximal inhibition (24.5%) at a relative high concentration (1.54 mmol/L). Moreover, BUC reacts with ROO(*); the relative ORAC(ROO) was found to be 0.34 micromol/L Trolox equivalents/micromol sample. The drug showed quenching of (1)O(2)-dependent 2,2,6,6-tetramethylpiperidine-N-oxide radical formation from 2,2,6,6-tetramethyl-piperidine (e.g. 90% inhibition was found at 1 mmol/L concentration). The results showed that BUC may directly scavenge ROS or inhibit reactions generating them. However, the drug may have pro-oxidant activity under some reaction conditions.     

Chemiluminescent detection and imaging of reactive oxygen species in live mouse skin exposed to UVA

The recent increase of ultraviolet (UV) rays on Earth due to the increasing size of the ozone hole is suggested to be harmful to life and to accelerate premature photoaging of the skin. The detrimental effects of UV radiation on the skin are associated with the generation of reactive oxygen species (ROS) such as superoxide anion radical (*O(-)(2)), hydrogen peroxide (H(2)O(2)), hydroxyl radical (*OH), and singlet oxygen ((1)O(2)). However, direct proof of such ROS produced in the skin under UV irradiation has been elusive. In this study, we report first in vivo detection and imaging of the generated ROS in the skin of live mice following UVA irradiation, in which both a sensitive and specific chemiluminescence probe (CLA) and an ultralow-light-imaging apparatus with a CCD camera were used. In addition, we found that *O(-)(2) is formed spontaneously and (1)O(2) is generated in the UVA-irradiated skin. This method should be useful not only for noninvasive investigation of the spatial distribution and quantitative determination of ROS in the skin of live animals, but also for in vivo evaluation of the protective ability of free radical scavengers and antioxidants.     

Antinucleosome antibody-modified liposomes and lipid-core micelles for tumor-targeted delivery of therapeutic and diagnostic agents

Liposomes and lipid-core micelles prepared of polyethylene glycol-phosphatidylethanolamine (PEG-PE) conjugates have been modified with nucleosome-specific monoclonal antinuclear autoantibody (ANA) 2C5 (mAb 2C5) specifically recognizing a broad variety of cancer cells through the cancer cell surface-bound nucleosomes. mAb 2C5 preserves its specific properties upon the binding with the lipid-based pharmaceutical nanocarriers, and 2C5-modified immunoliposomes and immunomicelles demonstrate an enhanced binding with tumor cells both in vitro and in vivo. We have investigated the delivery of therapeutic and diagnostic agents with such tumor-targeted immunoliposomes and immunomicelles to various tumors in vivo and in vitro. Both lipid-based nanocarriers provided enhanced tumor delivery of imaging agents ((111)In) and antitumor drugs (doxorubicin and photodynamic therapy agents) to tumor cells under different experimental settings. Pharmaceutical lipid-based nanoparticular carriers modified with mAb 2C5 could represent universal systems for tumor-specific delivery of various soluble and insoluble pharmaceuticals.